Posted by: Dan | August 23, 2007

Centriole Biogenesis: Polo-like Kinase as a vital factor?

I’ve been reading up on centriole biogenesis and centrosome duplication – look for more posts from myself on topics such as this: Plk4-Induced Centriole Biogenesis in Human Cells [Dev Cell. 2007 Aug;13(2):190-202]. From the introduction:

We have previously shown that overexpression of Plk4 in human cells causes the recruitment of electron-dense material onto the proximal walls of parental centrioles (Habedanck et al., 2005), suggesting that Plk4 is able to trigger procentriole formation. Here, we have used a cell line allowing the temporally controlled expression of Plk4 to study the formation of centrioles in human cells. We show that Plk4 triggers the simultaneous formation of multiple procentrioles around each pre-existing centriole. These multiple centrioles form during S phase and persist as flower-like structures throughout G2 and M phase before they disperse in response to disengagement during mitotic exit, giving rise to a typical centriole amplification phenotype. Through siRNA-mediated depletion of individual centrosomal proteins, we have identified several gene products important for Plk4-controlled centriole biogenesis and assigned individual proteins to distinct steps in the assembly pathway. Finally, we have been able to correlate these functional data with morphological analyses using immunoelectron microscopy. Taken together, these results provide a first molecular analysis of centriole formation in human cells.


Responses

  1. Hi Dan,
    It looks like MikeGene and company are distracted with this stupid movie coming out. Between work and the futility of this dualling philosophies, I am losing focus fast. Forgive me for lacking the motivation for continuing our previous discussions.

    However, MikeGene also brought up a discussion of Kinase. It revolved around this paper…
    Evidence for a Minimal Eukaryotic Phosphoproteome?

    I am presuming MikeGene was looking at it as support for front loading. I found this part interesting…

    Table 4 shows the distribution of peptide substrates with regard to the molecular functions of their source proteins… These data suggest that the phosphorylation events of this minimal phosphoproteome are associated with cell homeostasis; DNA replication, organisation, and stability; RNA translation; cytoskeletal organisation; motility; transmembrane ion transport; and signal transduction.

    I have picked up enough understanding to recognize how quantum mechanics could play a key role in each item on the author’s list, especially “cytoskeletal organisation” (microtubules).

    Here is something from a paper titled…
    Modulation of a Metabolic Network by Cytoskeletal Organisation and Dynamics

    Cytoskeletal dynamics play an essential role in sensing and responding to osmotic stress. It is likely that the spatial organisation and orientation of cytoskeletal proteins are modulating gene expression, signal transduction, and metabolic fluxes. Microtubules, actin microfilaments, and intermediate filaments represent a large surface area in the cell (estimated to be 3000 micrometres square per mammalian cell). This large surface area provides an interface for enzyme and other protein binding.

    Excuse me if you have no interest in either of the above. I found them in a vain attempt to engage the more moderate ID proponents at Telic Thoughts to discuss science. It is beginning to look more and more like I am wasting my time there.

    It is no secret at Telic Thoughts that I am concerned that if push comes to shove, the religious majority is capable of unethically ignoring laws (including the constitution) to protect their faith from the fear of scientific advancement. Having us all embrace Gould’s NOMA is a preferrable solution, IMO.

    However, maybe we will get lucky this time and the dark ages won’t last 1000 years and be isolated to only one country.

    Do what you will what I provided. I am curious to confirm that “Cytoskeletal Organisation” is talking about organs (like our skin is an organ), not organization, right?

    Is this related to the biogenesis you were talking about?

  2. TP,
    Indeed – MikeGene’s prediction of a smear campaign against Ben Stein is nothing short of stupid. Of course Stein’ll be called a fool for being a fool, but that’s a statement of fact by definition, not a smear campaign.

    Anyway, yes, I agree that his repeated use of evidence for common descent as evidence for frontloading is unsupported and anything but science. I’m not surprised to hear that you receive deaf ears to trying to discuss actual science with them – such has long been my conclusion.

    But, that’s all an aside to the topic at hand, which you relate to with kinases and microtubules. As such, your first quote from the paper on the minimal eukaryotic phosphoproteome. (another aside – Somewhere in my post archive I have a similarly-emphasized post on the evolution of the eukaryotic kinome) The evolution of the ‘phosphoproteome does indeed appear to be correlated with such functions, with a slew of additional functions being added to the original subset upon the advent of multicellularity. The clear implication is that an original kinase, adapted from a non-kinase predecessor, was itself co-opted to perform a host of additional functions, which arose under conditions that favored kinases being co-opted instead of other proteins.

    No need for ‘frontloading’ there.

    Regarding the second paper, on modulation of metabolic networks by cytoskeletal organization, I’m not sure how you interpret that paper. My interpretation though, is that yes, such complex (but natural) chemical organization (that’s what microtubules are, really: macromolecular chemicals) directs evolution of such networks, but only in the sense that certain chemical reactions are directed to chemically-determined outcomes.

    Again, no need for ‘frontloading’… Very interesting science however.

    The thought had occurred to me to specifically address MikeGene’s post (as the linked paper is interesting), but was frankly a little bored at the thought of taking on every bit he asserts with a blank-face (or so I imagine) to be frontloaded.

    In any case, look for more discussions from me on papers of other proteins potentially involved in centrosome duplication! That, and how the bipolar spindle is formed in mitosis, is more of what I was referring to with ‘centriole biogenesis,’ which is the process by which the single centrosome of quiescent cells duplicates and sets up chromosome segregation in anaphase.

  3. Oh, and to your comment of NOMA – agreed, that would be a wise and compromising tactic. The trouble is, I can’t bring myself to agree with it myself, however good a political tactic it may be.

  4. […] 30th, 2007 by Dan A week ago, I mentioned Plk4 as a kinase implicated in centrosome duplication. An array of other factors appear to be involved […]


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