Multifunctional Signals
by MikeGeneA classic example of a receptor tyrosine kinase receptor is the insulin receptor. Most people are familiar with insulin because of diabetes, a disease that is associated with high blood sugar. Basically, insulin is a protein hormone that is secreted by endocrines cells in the pancreas. Once the insulin enters the blood, it can specifically bind to insulin receptors on the cells of various tissues, triggering those cells to import glucose. Diabetes can be caused either by either a defect in insulin production (type I) or a defect with the insulin receptors (type II). Either way, failure to import glucose from the blood leaves high levels of glucose in the blood - high blood sugar.
Well, we can make a slight detour on our trip through the rabbit hole given the announcement of some new research yesterday. It turns out that insulin is a multifunctional signal molecule, highlighting the modularity of the whole system:
A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) has demonstrated for the first time in living animals that insulin receptors in the brain can initiate signaling that regulates both the structure and function of neural circuits.
The finding suggests a significant role for this class of receptors and perhaps for insulin, not only in brain development, but also in cognition and in pathological processes in which cognition is impaired, as in Alzheimer's disease, for example.
Insulin receptors on the surface of cells throughout the body have long been understood to play a central role in controlling metabolism through the regulation of glucose. When a molecule of insulin, a hormone, "docks" with the receptor, a complex signaling cascade is set in motion inside a cell, culminating in the cell's uptake of insulin.
Although insulin receptors are observed in certain parts of the mammalian brain, most scientists, until a few years ago, had assumed the organ was "insulin-insensitive," knowing that glucose could be taken up by brain cells without the involvement of either insulin or insulin receptors.
In recent years, however, it has been shown that the brain is indeed an insulin target, and in cell-culture experiments that insulin receptor signaling in neurons can have an impact on the formation and development of neural circuits. This had never been demonstrated in living organisms until it was shown in experiments performed in the laboratory of CSHL Professor Hollis Cline, Ph.D., and reported this week in the journal Neuron.
Pretty cool (although not entirely surprising given what we know about insulin in other species -insulin plays a role in neural development in Drosophila). But surely the Rabbit has something more intriguing to show us…….
June 19th, 2008 at 11:08 pm
It's more than a suspicion:
The Role of Insulin in the Development of Alzheimer's Disease
Recent research suggests that a failure in insulin processing in the brain may contribute to the development of Alzheimer's disease. Dr. Sam Grandy, Chair of the Medical and Scientific Advisory Council of the Alzheimer's Association, talks about this intriguing new insight.
Comment by Bradford — June 19, 2008 @ 11:08 pm
June 20th, 2008 at 8:51 am
Reaction to irreducible complexity frequently alleges that it is an argument that evolution is impossible and therefore anti-science. Yet it can be viewed as a challenge to order a series of events from starting point to outcome through correct sequencing. Clues as to correct pathways would have indicators impacting function. Diseases can be thought of as natural function disablements- nature's knock-outs. How does that signaling cascade come about? Which elements in it are relatively unique and which ones appear to have multiple uses? Behe's observations can be thought provoking.
Comment by Bradford — June 20, 2008 @ 8:51 am
June 20th, 2008 at 10:09 am
Behe's claim is that "an irreducibly complex biological system, if there is such a thing, would be a powerful challenge to Darwinian evolution." In fact, "interlocking complexity" was originally *predicted* as a consequence of evolutionary processes by Hermann Muller in 1918.
Comment by Zachriel — June 20, 2008 @ 10:09 am
June 20th, 2008 at 11:00 am
What are the similarities between Behe's notion of IC and Muller's notion of "interlocking complexity".
Also, how does evolutionary processes entail a system with "interlocking complexity" It's one thing to say that something predicts it, another to show that given EP, "interlocking complexity".
Was Muller's notion of "interlocking complexity" directed towards the behavior of proteins at a molecular level?
X-ray crystallography wasn't even around before the 1960s. Quite the amazing prediction in 1918 that proteins would come together via non-covalent bonds and for interlocking structures. Didn't Linus Pauling receive a Noble Prize for his work on weak bonds and the role they played in protein folding…… in the 1930s?
Comment by Doug — June 20, 2008 @ 11:00 am
June 20th, 2008 at 11:10 am
From the link supplied by Zachriel:
An increase in the genetic load is problematic for a paradigm of increasing complexity. This given a complete complement of genetic repair mechanisms. An evolutionary process, devoid of such repair mechanisms, is fertile ground for evidence of front loading in my view.
Comment by Bradford — June 20, 2008 @ 11:10 am
June 20th, 2008 at 11:24 am
I found this on talk.origins:
When he refers to complicated machinery and 'whole machinery', what do you think he is referencing, Zach? Proteins that come together to form a functioning complex that carries out a particular task? Held together by covalent bonds and non-covalent forces, matching because of complementary surfaces?
Comment by Doug — June 20, 2008 @ 11:24 am
June 20th, 2008 at 11:36 am
Sorry Mike,
You can memory hole my comments. We're not talking about IC and have been bring the conversation in that direction…. sorry.
Comment by Doug — June 20, 2008 @ 11:36 am
June 20th, 2008 at 12:04 pm
Doug, the post is filed under the front loading category. It's my view that IC can be an indicator of FL. If that's the case then the two concepts are related.
Comment by Bradford — June 20, 2008 @ 12:04 pm
June 20th, 2008 at 12:12 pm
Hi Bradford,
I was really only referencing my posts. After I read through the topic and the reply posts again mine just seemed to tangent off in a direction that could serve to sidetrack the discussion.
Comment by Doug — June 20, 2008 @ 12:12 pm
June 20th, 2008 at 12:36 pm
Not a probem, Doug. In fact, I'm very glad Zachriel brought this up, although I don't think he'll be comfortable with my take on it - hopefully, later tonight.
Comment by MikeGene — June 20, 2008 @ 12:36 pm
June 20th, 2008 at 1:26 pm
If you're cool with it.
Thanks.
Where's TP?
We're doing science!!
Comment by Doug — June 20, 2008 @ 1:26 pm
June 20th, 2008 at 6:13 pm
The concept of interlocking complexity would apply to many such evolutionary systems, but Muller is referring to how genes influence the development of specific morphological and physiological traits.
A simple example is where we have a mechanism
Pwhich is sufficient unto itself, but to whichQhas been added as a catalyst enhancing the reaction.Pmight then evolve to a greater level of efficiency, but one that requiresQ. This is a typical example of how specialization leads to interlocking complexity.From this, Muller argues that most (non-neutral) mutations should be detrimental. They disturb the finely-tuned complex.
Comment by Zachriel — June 20, 2008 @ 6:13 pm
June 22nd, 2008 at 7:54 pm
Hi Doug,
You are correct in noting that Muller's discussion is not directed towards the behavior of proteins at a molecular level. He is not talking about the type of complexity I describe on page 216 in The Design Matrix. In fact, we know that Muller's description of evolution did not lead scientists to anticipate this type of complexity (see p. 13). Muller is talking about the whole organism as the "machine" (which, as seen from pp. 101-103 of TDM, is not relevant). What he is essentially describing is a whole organism as an interlocking mass of complexity such that lethals should have been "among the commonest forms of mutants" and "we should expect very many, if not most, mutations to result in lethal factors, and of the rest, the majority should be "semi-lethal" or at least disadvantageous in the struggle for life." In other words, a non-telic view of evolution would lead us to expect that organisms should be a Rube Goldberg machine, a hodgepodge of factors tightly connected through a long history of co-evolutionary selection. What Muller and early views of evolution did not expect was what we found "“ that life is more rational than this; than life is built around the design principle of modularity (see pp. 167-169).
Comment by MikeGene — June 22, 2008 @ 7:54 pm
July 9th, 2008 at 10:18 am
[...] We have also seen that receptor tyrosine kinases (RTK) would play important roles in facilitating the evolution of multicellular life. Added to this is the recent discovery that one example of an RTK, the insulin receptor, plays an important role, along with its ligand insulin, in the development of the nervous system. [...]
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