Gold in dem holes?

Me thinks da bunny has dug up a little goldmine. In the previous essay, I shared what I uncovered about the components of adherens junctions. So let’s get up to speed about these structures. I told you they are used to connect cells together to form the sheets of cells known as epithelial tissue. Here are some more facts about these structures:

Adherens junctions provide strong mechanical attachments between adjacent cells.
• They hold cardiac muscle cells tightly together as the heart expands and contracts.
• They hold epithelial cells together.
• They seem to be responsible for contact inhibition.
• Some adherens junctions are present in narrow bands connecting adjacent cells.
• Others are present in discrete patches holding the cells together.

Adherens junctions are built from:
• cadherins — transmembrane proteins (shown in red) whose
o extracellular segments bind to each other and
o whose intracellular segments bind to
• catenins (yellow). Catenins are connected to actin filaments


Now, as I have shown, all the major components of these structures that are used to form multicellular organisms have homologs that exist in unicellular organisms. But the most interesting finding is the homolog for human beta-catenin in the green algae, Volvox carteri. Volvox is a actually a multicellular organism,

a fact that is going to make this rabbit hole very interesting later on.

But let’s lay out some bare information about this protein, beta-catenin. I informed you that it is a key link that connects the cytoskeleton (universal in eukaryotes) to the cadherins (membrane proteins that connect cells together). Here’s some more:

β-catenin is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. β-catenin also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete.[2]

Recent evidence suggests that β-catenin plays an important role in various aspects of liver biology including liver development (both embryonic and postnatal), liver regeneration following partial hepatectomy, HGF-induced hepatomegaly, liver zonation, and pathogenesis of liver cancer.[3]

To see how important this protein is, consider the figure below that shows the various circuitry that connects the membrane to various activity in the cell, including the expression of genes:

You can see the cadherins as the yellow lines in the two gray lines (the membrane). Connected to them are the blue circles, which represent the beta-catenins. My, they are involved everywhere. They link to the receptor tyrosine kinases (once thought to be specific to metazoans, as we have discussed). They are linked to endocytosis, the process of absorbing material into the cell. And they are linked to differentiation.

In fact, here’s a paper that outlines the importance of this protein in metazoan evolution:

Nature. 2003 Nov 27;426(6965):446-50.
An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation.

Wikramanayake AH, Hong M, Lee PN, Pang K, Byrum CA, Bince JM, Xu R, Martindale MQ.

The human oncogene beta-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity, formation of germ layers, neural patterning, spindle orientation and gap junction communication, but the ancestral function of beta-catenin remains unclear. In many animal embryos, activation of beta-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation, raising the possibility that asymmetric activation of beta-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of beta-catenin is involved in axial identity and/or germ layer formation in ‘pre-bilaterians’, we examined the in vivo distribution, stability and function of beta-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta-catenin is differentially stabilized along the oral-aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.

Now, let’s go back to the fact that human beta-catenin appears to be homologous to an undescribed protein in Volvox. Why is this so exciting? Consider the phylogenetic tree for all eukaryotes:

If this protein is found in both green algae and metazoans, then when was the last time they shared a common ancestor? Simply trace the lineages lines to see where they meet. What’s that? It looks like we can make a reasonable case that beta-catenins, used to connect cells together and to differentiate them during embryonic development, had a homolog that existed in the last common ancestor of all eukaryotes!

So let’s next nail down the homologous relationship and then watch the story become even more interesting.

One response to “Gold in dem holes?

  1. Pingback: The Adherens Junction Homology Goes Deep |

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