Details Of Nuclear Pore Complex With Spin
| January 31, 2008 | Posted by idnet.com.au under Intelligent Design |
(Credit: Image courtesy of Rockefeller University)
From ScienceDaily (Jan. 30, 2008) A cell’s membrane-bound nucleus uses hundreds to thousands of nuclear pores as its gatekeepers, selective membrane channels that are responsible for regulating the material that goes to and from a cell’s DNA. Rockefeller scientists have nailed down the first complete molecular picture of this huge, 450-protein pore and their findings provide a glimpse into how the nucleus itself first evolved.
The group gathered and analyzed massive amounts of data to come up with a rough draft of the structure of the nuclear pore.
The scientists’ results have given them a peek into the early evolution of eukaryotic cells. Compartmentalization was made possible by membranes and coating complexes, which act “like little hands” to grab, shape and stabilize membranes.
“We think that once the cells gained this coating complex, they ran with it and started to duplicate it and specialize it,”
“Evolution is a process of duplication and divergence,” Rockefeller professor Michael Rout says. He and his colleagues saw clear evidence of this. For every protein, there was another one that looked quite similar. “These are evidence of duplication events, showing that the evolution of the complicated nuclear pore was a more straightforward affair than previously thought. It’s made of many different variations of a theme of just one unit.”
“The nuclear pore is the communication device that the nucleus uses to communicate with the rest of the cell. And if you don’t understand how that works, you don’t understand a key part of how the cell works. You have to see the cell as a machine and understand all of its parts.”
refs Nature 450(7170): 683–694 (November 29, 2007): Nature 450(7170): 695–701 (November 29, 2007) Watch the movie here.
51 Responses to Details Of Nuclear Pore Complex With Spin
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hrun0815
Encourage you to look at:
Shape and Structure, From Engineering to Nature, Adrian Bejan, Cambridge, 2000.
Many of the principles he gives can be applied to NPCs in cells. (Bejan attributes some things to evolution, but without any basis for that. The principles naturally fit design.)
Pemberton & Paschal 2005 cite Kalab et al Science 2002 that:
This large RanGTP concentration gradient is worth exploring as to its ramifications.
(And the implications of not having that without a nucleus wall.)
What do you see as the implications of that gradient vs not having it?
Pemberton & Paschal 2005 comment that:
That supports the hypothesis of irreducible complexity.
Yes. It is worth studying. In fact, it is and has been studied extensively. It is crucial for selective and efficient transport. It is also know how the RanGTP gradient is being maintained.
In fact, the paper that you mention (by Pemberton and Paschal) gives quite an extensive view on a number of the implications of the gradient. Did you study the review? It actually gives so much detailed information on the ‘ramifications’ on the gradient: how RanGTP is maintained at high concentrations in the nucleus, how the enzymes that regulate the conversion of RanGTP/RanGDP are sequestered in the nucleus and the cytoplasm respectively, how the affinity of the different karypherin/cargo complexes to RanGTP/RanGDP regulates directional transport into and out of the nucleus, and how the RanGTP gradient is not only important for nucleo-cytoplasmic transport but also for formation of the spindle.
Did you have any other specific ‘ramifications’ in mind that ought to be explored but are not already?
I don’t have to look at implications of having or not having the gradient. It certainly has been experimentally tested. For example, it has been shown that by reversing the gradient transport can be reversed in its direction. Thus, biologists concluded that it is important for the directionality of transport. Numerous other experiments have been done and many of them are summarized and referenced in the Pemberton review.
I don’t see what you mean by ‘not having that without a nucleus wall’ though, so I can’t really reply to that.
It is known (and somewhat unsurprising) that a number of components of the transport machinery are essential for eukaryotic cells. I thought, though, there were much more specific requirement before something can be called irreducibly complex. It can be a little confusing, since there are apparently multiple definitions of IC.
However, no biologist that I know of, though, disagrees that there are numerous IC structures in cells if the most basic definition of IC is used (complex functional unit consisting of multiple well matched parts, each of which is essential to the function of the whole unit).
That’s why I said the following:
I’d still be interested in discussing this, since you point out in a number of posts that you hypothesize the NPC to be IC.
hrun0815
I am brainstorming/ exploring ways to apply design principles. Apologize for being a novice at the biochemistry. I have read Pemberton and Paschal’s review. Now to study/digest it.
Consider what would the impact be of reducing the gradient by 95%?:
E.g., possible design principles:
1) Energy is need for processes.
2) A given process rate requires a corresponding energy supply rate (power).
3) Energy supply rates below that will slow that process.
4) A given high energy supply rate is required to maintain a high process rate.
By
I was thinking of comparing process rates in the eukaryotic nucleus, eukaryotic cytoplasm, and in prokaryotic cells.
The difference may relate to size and design methods to accommodate scaling factors.
e.g., if eukaryotic cells are 1000 times larger than prokaryotic cells.
Can this high RanGTP gradient be needed to scale up in size?
DLH, very likely the directionality of transport would be impaired. I predict this because we know how the gradient affects transport and because we know the outcome of experiments where the gradient has actually been inversed.
Interestingly, I again don’t see a difference in what you would hypothesize from design principles and what biologists hypothesize and test from their non-teleological point of view.
Also the non-teleological researchers know that for processes to run you require energy. That is completely independent whether a designer created the NPC or whether the NPC evolved.
DLH, RanGTP is not a major factor in the overall energy flow and maintenance within a cell. And remember, we are talking here about a gradient of RanGTP, not GTP itself. As you are surely aware of, GTP is substantially smaller than the diffusion limit of the NPC, so it will be fairly evenly distributed across the nucleus and the cytoplasm.
Thus, I find it highly unlikely that this gradient ‘may relate to accomodate scaling factors’. Especially if we take into account that both prokaryotic and eukaryotic cells show quite the range in size. The smallest eukaryotic cells are less than a micrometer in diameter while the largest ones are over 100 micrometer in diameter (1 million fold difference). Interestingly, the largest bacteria have a diameter of 750 micrometer and are thus nearly 1 billion times larger than the smallest eukaryotic cell. Yet, still the small eukaryotic cell likely has the same RanGTP gradient for transport and spindle assembly, while the largest prokaryote does not.
I have quite direct question about this: How did you come up with this hypothesis? And upon further thought, do you think it is one that a group of researchers should seriously pursue?
Do you think it would maybe be more fruitful for researchers to simply look which proteins for example interact with RanGTP, which processes get messed up when you interfere with the gradient, what proteins and processes are required to maintain the gradient, …
With this approach researchers indeed found how the gradient drives selective transport and in addition how this gradient impacts the assembly of the mitotic spindle. And currently numerous times are delving further into the details at how exactly RanGTP impacts these processes and if there are others it impacts.
As an aside, unfortunately, you have not found the time to answer my question about what we could predict if we indeed confirmed that the NPC is IC. All I can say is that I am still very interested in discussing this topic. Maybe you could just let me know whether or not you agree that this is worth discussing.
hr0815
Thanks for the feedback.
Yes, I would like to explore the implications of “Irreducible Complexity”. Here are some preliminary thoughts.
(PS I am trying to get the links working)
You cited the definition of Irreducible Complexity:
We had noted system failure on lack of an irreducible component.
Lets now explore “multiple well matched parts”.
Consider: In what way is spacecraft design based on horses? See: What Is the Link Between a Horse’s Arse and Space Shuttles? – The oldest and the newest means of transportation, Lucian Dorneanu, Science Editor Softpedia
In summary, the shuttle booster rockets had to go through a tunnel on a 4′ 8.5″ standard gauge rail train, based on Liverpool and Manchester Railway, based on tramways, based on collier carts, based on wagon wheel ruts in Imperial Roman strata (“streets”) which were based on standardized Roman war chariots, which in turn were based on the width of the back end of the Roman war horse.
A key design principle is to use standardized parts with robust design tolerances. Thus rockets sized for safe tolerances in the tunnels based on standardized roman war chariots. In biochemistry, a corresponding example is the size of capillaries to fit Red Blood Cells (RBC) to transport oxygen via hemoglobin. E.g.,
The squeezing of red blood cells through capillaries with near-minimal diameters
D. Halpern a1 and T. W. Secomb Journal of Fluid Mechanics Digital Archive (1989), 203: 381-400
Axisymmetric motion of a file of red blood cells through capillaries, C. Pozrikidis, Phys. Fluids 17, 031503 (2005);
Modeling the flow of dense suspensions of deformable particles in three dimensions, Michael M. Dupin, Phys. Rev. E 75, 066707 (2007) (17 pages)
These proportionalities appear to scale with Red Blood Cell/Capillary size. E.g., see: Red blood cells: Centerpiece in the evolution of the vertebrate circulatory system Snyder, Gregory K, Sheafor, Brandon A, American Zoologist, Apr 1999
Mutations resulting in deformation of red blood cells can result in capillary blockage. E.g., in sickle cell disease.
Following are some examples of detailed modeling:
Mathematical and mechanical modeling of vaso-occlusion in sickle cell disease Higgins, John M., MSc. Thesis, Harvard University–MIT Division of Health Sciences and Technology.
This is one example of what happens when there is a change from the “well matched parts” of irreducible complex systems due to mutations.
Now apply this principle to Nuclear Pore Complexes and related transport mechanisms.
As with Red Blood Cells in capillaries, I expect there will be similar design criteria and consequent impacts of going outside such robust design boundaries in the transport mechanisms relative to the Nuclear Pore Complex sizes.
1) There will be a normal allowable size range for mediated transport.
2) There are tolerances for docking requirements of macromolecules onto the transport molecules.
I.e., transport plus load must fit within the Nuclear Pore Complex.
3) Larger molecules must be expressed inside the nucleus, or transported through the wall in components and assembled inside.
E.g., compare the international space station compared with the size limitation in the rocket payloads.
As we noted above, very few viable mutations suggests very tight tolerances on the dimensions involved in the transport mechanisms & nuclear pore complex.
For the loads, see: Naim et al.
“Passive and Facilitated Transport in Nuclear Pore Complexes is Largely Uncoupled.” J. Biological Chemistry Vol 282, No. 6, pp 3881-3888.
Modeling the flexibility of the mediated transport of macromolecules compared to the nuclear pore complex will be a key challenge.
As from Roman chariot to space shuttle booster, the mediated transport through the Nuclear Pore Complex has consequential design implications of maximum size for all related macromolecules that need to be transported through the cell nucleus wall.
hrun0815
Thanks for the clues on dimensions. I found the following on regulation of ATP transport:
ATP Transport Through a Single Mitochondrial Channel, VDAC, Studied by Current Fluctuation Analysis, Tatiana K. Rostovtseva* and Sergey M. Bezrukov, Biophys J, May 1998, p. 2365-2373, Vol. 74, No. 5
Following is another report exploring the large macromolecule mediated transport vs small molecule transport.
A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules. JBC Papers in Press, August 28, 2007, DOI 10.1074/jbc.M703720200, Armin Kramer1, Yvonne Ludwig, Victor Shahin, and Hans Oberleithner
hrun0815
One design principle is to
Preserve the design
Thus I expect the use of detailed error proofing and correction. This will become more important and the system becomes more complex.
I just realized that:
Tight physical tolerances in the nuclear pore complex & related transport mechanisms act as an effective proofing and error deleting mechanism.
i.e., by eliminating components with mutations causing physical changes outside the design boundaries. e.g., too big to fit, or where the docking station changes to no longer match the transporter’s docking station.
I expect this principle will apply elsewhere where materials must be transported through pores.
On your previous question of consequences of IC, I would put error proofing and deleting as one of the symptoms of being designed.
Restating ‘Well matched”:
Design parameters have critical tolerances.
The concept Irreducibly Complex overlaps the design summary:
Life is Regulated
DLH, locking at the Pemberton and Paschal review, do you think any of these three hypothesis differ in any way from what non-teleological researchers might hypothesize about NPC function (or in fact have already extensively studied in the past 20 odd years)?
Frankly, so far I have seen only three types of ‘teleological predictions/hypothesis’ about the NPC in this thread:
1) predictions that are already invalidated by observed facts (e.g. RanGTP gradient important for scaling)
2) predictions that have already been made and confirmed by non-teleological researchers (e.g. redundancy of NPC, cargo size limitations, …)
3) predictions that are currently under investigation by non-teleological researchers
Does it come as a surprise to you that the teleological ID approach is apparently no different from the non-teleological biological approach?
I don’t understand this sentence. Could you clarify?
If I understand you right, this is not so much a prediction about the NPC as it is a prediction about structures assembled from components that passed through the NPC.
Again, do you really think that a teleological approach is required to hypothesize that the size of the NPC limits the size of components that can be utilized in the cell (if these components are required to be transported through the NPC)?
Why would this very general statement be obviously true if the NPC was designed but NOT obviously true if the NPC was NOT designed? If the statement is obviously true IRRESPECTIVE of the origin of the NPC, then the non-teleological approach is (at least in this case) no detriment to this research, right.
This is what is really puzzling me, the fact that whether or not the NPC is designed apparently does not have any bearing on the research on the structure and function of the NPC and on the consequences for the cell due to the structure and function of the NPC.
Why would error proofing follow from IC? Are there no IC structures that come without error proofing?
I am surprised at the broad generality of these statements. I certainly agree with both of them. Design parameters do have critical tolerances and life is regulated.
But who would disagree? ALL components of a functional unit have critical tolerances. For that to be true they don’t have to be designed. For example, I bet that for every component of anything failure will occur if the temperature is increased sufficiently. Thus, there is a critical tolerance. What does that specifically tell us about studying the NPC from a teleological point of view?
In the end, I guess, it comes back to what I said in my previous post: Does it come as a surprise to you that the teleological ID approach (to study e.g. the NPC) is apparently no different from the non-teleological biological approach?
hrun0815
I challenge you to examine whether research allegedly planned from an “atelic” perspective – without purpose or design – is actually without design.
I submit that people are so used to recognizing and practicing design that what you say is “non-tellic” incorporates design through and through.
e.g., consider “atelic” experiments that are not allowed to use any “Design of experiment”, since that by definition includes design in the experiment.
On Life is Regulated
Do you know of any neo-Darwinian model that shows that the four laws of nature that can explain regulation?
- Especially regulation in the first cell?
Yet regulation is inherent in most electrical and mechanical engineering designs. Thus, regulation appears to be a natural result of intelligent causes.
So you are no back to asserting that these smart folks are in a way unknowingly performing their research from a design perspective?
See comment #23, #24 and #25. I can’t argue against this in any way. All I have to say is this: the ‘atelic’ perspective does not deny functionality. All the predictions from a design perspective you have made in this thread follow equally from an atelic point of view. As I said, nobody denies that the NPC has a function and performs it well. Whether some being created the NPC to perform this function is immaterial to studying said function.
And I think that becomes abundantly clear when we compare your suggestions to what is actually done.
What do you mean? Biologists study regulation all the time without resorting to any mythical power that would fall outside any law of nature. (Regulation gets nearly 1 million hits on PubMed.)
So IF this is indeed true and if, as we found in this thread, the researchers are already performing all the research that would be indicated from a teleological perspective, then the scientific research at our Universities should be in pretty good shape, right?
Now, if we found a good hypothesis from a design perspective on the NPC that is not actively being pursued (or has already been performed), then things would be quite different.
However, I still am quite perplexed that you commend these researchers multiple times on this brilliant research project, yet still consider them sufficiently ‘confused’ that they can publish a) a paper that deals exclusively with the evolution of the NPC from a more primitive structure and b) perform all their research from a design perspective.
PS, I just saw this part of your post:
Are you suggesting that the design of an experiment by a researcher is already a case of using a design perspective or a teleological approach? I must be misunderstanding this.
hrun0815
There are multiple overlapping issues.
1) ID as a theory that can detect intelligent causation.
2) ID as applied as an origins theory to detect an intelligent designer evident in biological systems and/or cosmological systems.
3) Developing ID as a descriptive theory of nature.
4) Developing ID to then have predictive power.
5) Conducting research based on ID predictions.
6) Distinguishing ID from atellic origin theories, eg acknowledging microevolution while differing non macroevolution.
7) Distinguishing research conducted to test tellic vs atellic predictions.
My challenge on “atelic” experiments is to step back and realize how ingrained design is to try to actually envision “atelic” systems. Design of experiment (DOE) is so natural that thinking how to do an experiment without it is to help think what atelic really means.
e.g. take measurements at random times and with random parameter settings. What is the probability of identifying useful results?
In some ways Darwin was begging the question by starting with living reproducing systems and applying RM & NS, without examining if that foundation was from abiogenesis or revealed design.
I hold that natural selection incorporates “cells come from cells” together with numerous regulated systems, which are evidence of design.
Thus the research tasks of:
R1) Search for symptoms of regulation.
R2) If found then search for the components of that regulated systems
are inherently from a design perspective, not an atelic perspective.
Thus my exploring what parameters vary by concentration across the nucleus membrane and/or by time was searching for regulated systems.
On the NPC research, distinguish between the modeling / experimental results, and then the effort to fit those results into an “evolutionary” perspective. Many of the arguments given can equally be described from an ID perspective.
Examine where models were shown that would give any quantitative estimate of how that could come about, or how the nucleus could function while random mutation and supposed natural selection achieved this wondrous Nuclear Pore Complex & associated Transport structures. See Genomic Entropy and the Mystery of the Genome by John Sanford. Statistically mutations destroy far faster than possible “positive” mutations – especially if you do not have a self reproducing system to begin with.
Ok, DLH, I think we have arrived at an impasse. I can truly not believe that you are arguing that researchers who content that, for example the NPC is a product of evolution and not of a designing entity would have to study the NPC by taking ‘measurements at random times and with random parameter settings’.
Are you really serious about this? Is this how intelligent design proponents define experiments from an atelic point of view?
If that is the case, then you are absolutely right. All those biologists perform experiments from a ‘design perspective’. After all, they are intelligent and they design experiments. Voila, Intelligent Design.
But if that is the case, then ID is alive and well, performed every single day in tens of thousands of biology labs throughout the world.
And, in the end, it still strengthens my point: What would be the difference between the research being done right now (e.g. on the NPC) and research from a ‘design perspective’.
I’d be happy (is anybody is still following this thread) for other design advocates to clarify if they share DLH’s view on ‘atelic’ research.
DLH
See stochastic events based on the Strong Nuclear force, Weak nuclear force, electromagnetism and gravity.
hrun0815
Yes, but I expect 99.99% of them have not logically or quantitatively considered how such regulatory systems could arise from atelic presuppositions. Everyone is so used to controlled or regulated systems, that they have not grasped what it would mean to start without ANY regulation, and thus with no self reproducing cell.
hrun0815
I agree. I am not expecting researchers to conduct “atelic” experiments. Just to think of even how to conduct an experiment in an atelic fashion to begin to faintly grasp what “atelic” means.
I would still expect researchers to do prepare professional Design Of Experiments, when testing atelic theories. See for example the quantitative measurement of the probability of single and them multiple mutations persisting and being fixed in reproducing microorganisms.
You earlier said:
BUT do they dare publish that and state that there is no Neo-Darwinian method known to achieve those? Ah, there is the rub.
And do any dare mention that ID might also be considered?
Instead, we have vociferous opposition to any mention of irreducible complexity because of its implications –
BUT instead we have mandated RM & NS because of its atheistic implications. Such is the fascist control of atheistic presuppositions over majority science.
Much of the discussion has been jumping into the middle of a particular example without the benefit of the larger picture and developed goals and guiding design principles. I will have to work on writing that up to show how this all fits together. Apologize that this blog has been much more stream of consciousness bits and pieces.
On “well matched”, See Behe’s Darwin’s Black Box and his explanation of the components of the mouse trap needing to be sized to each other. Many of the things that may seem obvious on the Nuclear Pore relative sizing, need to be examined and detailed when you are positing atelic vs telic design considerations.
Particularly, how do those relative well fitting parts come about all together in the right time in the right order with assembly methods and structures etc.
You are absolutely correct. On a day-to-day basis, most biological researchers don’t concern themselves much with were the first cell might have come from. I don’t see what that has to do with the function and evolution of the NPC.
As I said, you can study the function of the NPC independently of where it came from. And it appears that the approach (whether a designer designed the first cell or if it came about by other means) would change much one way or another.
Unfortunately, I have to respectfully disagree with you here. Think about it: Do you believe that Rout et al think that the NPC is assembled from well matched components that (if reduced by mutation to the smallest functional core) would cease functioning if a further component was removed? Certainly! Indeed, many researchers are performing those very same experiments. However, Rout et al also publish a whole paper on the evolution of the NPC from coated vesicles.
So, none of the facts get denied and no RM+NS is being mandated. Merely, the conclusion that IC systems are impossible to generate by evolutionary processes are denied.
I’m not here to rehash that argument. Clearly that would go beyond this thread.
Suffice it to say, I think this thread has clearly shown that the researchers are already studying all the possible hypothesis that you proposed from a design perspective. You claim this is due to an implicit ‘design approach’ by the researchers. I doubt that this is the case. But, as I said, it is impossible to disprove.
We find ourselves now in a position where I claim the researchers clearly don’t have a ‘design perspective’. You claim that the researchers do the research because they completely internalized the ‘design perspective’. In either case, it seems that we both agree that the ‘design perspective’ would not change the NPC research.
I find that rather surprising, but I’m happy we at least can agree on that.
What are the proteins and transport mechanisms related to NPC
HOW do they work.
What are the material and energy flows? etc.
These are all generic research.
To test whether they have arisen via evolution vs via design:
ID would predict that systems are regulated, and search for those.
I know of no basis in RM & NS to predict regulation other than assuming it exists because self reproducing life is presumed.
But I claim that begs the question.
ID would expect selective dedicated transport mechanisms rather than diffusion as more energy and material efficient.
Evolution can claim that this arises out of “natural selection”, but the probabilities of that quantitatively happening are astronomically remote beyond all credibility.
IS would posit that components are well designed and matching, and that mutations will almost always cause degradation or destruction of function.
e.g. Sanford cites published estimates of 1 million to 1 for harmful vs beneficial mutations.
Knock out experiments can efficiently show essentiality.
The Online Mendellian Inheritance in Man documents the “experiments” and harmful consequences of mutations in peoples lives. (18,000 entries last I checked.)
Evolution needs small gradual changes with positive selection for each one. The biochemical evidence of harmful impact of mutations and the cumulation of near neutral mutations flies against all evolutionary hand waving.
Finding such small gradual beneficial changes if they exist would quickly consume all research budgets and computing power for even very small systems.
Unless the NPC or transport structures are related to disease, I would not expect much quantitative effort in exploring large numbers of mutations. I look more for the 1000 genome project to provide quantitative results to then see what mutations have survived.
More later on stoichiometric ratios of pores to DNA as an ID predictive hypothesis.
DLH, I am glad that from post to post we agree more and more. Previously, you asserted that all these approaches were specific to a design perspective or teleological approach. But it’s great we now agree they are just generic research based on trying to figure out how stuff works. Great!
So again (I’m sorry if it appears that I am repeating myself), how would ID research differ from the research currently underway. Considering that there are nearly 1 million publications in PubMed alone that contain the word ‘regulation’, clearly all those researchers without a ‘design perspective’ are aware that a) life is regulated and b) that it’s an important topic to study.
DLH, remember that without self reproducing life there can be no RM&NS– So of course RM&NS presumes the presence of self reproducing life.
Well, funny thing is, the NPC actually works by diffusion. It’s very clearly explained in the NPC Nature papers and in the Pemberton review. That’s the interesting part– the NPC does NOT work how humans would go about designing a transporter. But in the end, that’s somewhat irrelevant.
So now we are reduced to discussing what evolution can and can not do. I agree those are interesting topics, but not really what I set out to argue about here. The premise of your first post was to look at the data presented in these papers from an ID perspective. So far I have not seen a single thing that would indicate that this perspective brings anything new to the table (other than the NPC could not have evolved).
I’ll be here, waiting.
Re-reading my last comment I realized that the last sentence came out sounding wrong.
I am very interested in any prediction/hypothesis that can be developed from an ID perspective that is not already pursued by biologists. And, I am certain, so are researchers that work on the NPC. In the end, researchers are much more result-driven (rather than ideology driven). If they have a chance to figure out something important about the function of the NPC within the cell, they will jump on that opportunity, irrespective of where the idea came from (ID proponent, Engineer, Biologist, Mathematician, …).