Phylogenetic analysis of the NEEP21/calcyon/P19 family of endocytic proteins: evidence for functional evolution in the vertebrate CNS.

摘要: Endocytosis and vesicle trafficking are required for optimal neural transmission. Yet, little is currently known about the evolution of neuronal proteins regulating these processes. Here, we report first phylogenetic study NEEP21, calcyon, P19, a family implicated in synaptic receptor endocytosis recycling, as well membrane protein somatodendritic axonal compartments differentiated neurons. Database searches identified orthologs P19 NEEP21 bony fish, but not urochordate or invertebrate phyla. Calcyon were only retrieved from mammalian databases distant relatives teleost fish. In situ localization zebrafish ortholog, extant progenitor gene family, revealed CNS specific expression pattern. Based on non-synonymous nucleotide substitution rates, calcyon genes appear to be under less intense negative selective pressure. Indeed, functional group II WW domain binding motif was detected primate human non-primate orthologs. Sequencing 80 subjects single polymorphism that abrogated binding. Altogether, our data indicate NEEP21/calcyon/P19 emerged, underwent two rounds duplication relatively late metazoan (but early vertebrate at latest). As studies suggest play related, distinct roles synapses, neurons general, propose arose chordates support more diverse range behavioral responses.