I have previously tried to show you that it is quite plausible to propose that a protein essential in two multicellular processes existed in the last common ancestor of all eukaryotes. Thus, this could be one front-loaded feature to these cells that would, sooner or later, help to nudge animal life into existence. But if it is too difficult to believe that something like beta-catenin is as old as the eukaryotic cell itself, let me make it even more clear that beta-catenin was always in the cards. How? By showing you that even if beta-catenin is not quite as ancient as I propose, its very existence was front-loaded by the existence of a remarkably similar homolog – alpha importins.
What are alpha importins? First, you need to step back a moment and reconsider the design of the eukaryotic cell – the nucleus, which contains the genetic material (genotype) is separated from the ribosomes which ultimately express the genetic material (phenotype) by a membrane. So, when it comes to the various proteins that interact with the DNA, they are first synthesized by the ribosomes out in the cytoplasm and then they must be shuttled into the nucleus. The alpha importins come into play when it comes to shuttling proteins into the nucleus. Their job is to recognize signals on newly made proteins that act as passwords for access into the nucleus. Once the alpha importins find the signal (known as the nuclear localization signal (NLS)) on some cargo protein that is supposed to be in the nucleus, they bind to it and then interact with another protein known as beta importin. Together, the complex of alpha importin + beta importin + cargo enter the nucleus through the nuclear pore complex. Here’s a figure to help you visualize it:
Given that alpha importins play a basic and crucial role in the eukaryotic cell by allowing proteins entry into the nucleus, it is quite reasonable to proposed that alpha importins are as old as the eukaryotic cell itself. And as far as I have been able to determine, they are universal among eukaryotes. Also, their sequence is highly conserved. For example, when alpha importin from rats is compared to those from the green algae Chlamydomonas reinhardtii, 259/540 (48%) positions contain the same amino acid and 351/540 (65%) positions contain amino acids with the same or similar properties.
So why think alpha importins and beta catenins are related? For starters, go back to my table of beta catenin homologs in unicellular, eukaryotic organisms. As we saw, by using the Volvox version of beta catenin to probe data bases, I retrieved lots of hypothetical proteins and a known beta catenin homolog– aardvark. But the homologs from Theileria parva, Perkinsus marinus, and Leishmania major were all alpha importins. If we accept the Volvox protein as a beta catenin, then we have homologs from three different protozoa with E values ranging from 3.00E-17 to 1.00E-19.
What’s even more striking is the fact that both alpha importins and beta catenins are composed of a series of nine or so Arm repeats arranged in a similar many. Consider the CDD representation of the Arm domains from the rat alpha importin:
Notice the pattern of nine Arm repeats broken into three sets with the second and third set overlapping. The domain attached to the front end is IBB and it is the region that sticks to the beta importin.
Now, consider what a rice alpha importin looks like:
Or alpha importin from fruit flies:
Or the green algae, Chlamydomonas:
How about one of our homologs mentioned above, the protozoan Perkinsus marinus:
Or another homolog from Theileria parva:
Or the protozoan Leishmania major:
Starting to notice a pattern among vertebrates, invertebrates, plants, algae, and protozoa alpha importins?
So what is the domain organization of human beta catenin again? Oh yeah, here it is:
Let’s make an even stronger case in the next essay.