Essential tetraspanin functions in the vertebrate retina

Abstract

This chapter summarizes current knowledge and reviews recent findings regarding the structure, function and importance of tetraspanins in the vertebrate neural retina. Since inherited defects in several human tetraspanins, including tetraspanin12 and peripherin-2/rds, are well documented to cause sight-robbing ocular diseases, these molecules are of significant interest from both basic science and clinical perspectives. In the retina, as is the case more generally, tetraspanin superfamily members serve diverse biological functions, but have in common the capacity to organize lateral interactions within cellular membranes. Proteins characterized to date can also display several distinctive properties, including: a high degree of cell-type specifi city, a reduced tendency to participate in interaction webs, and an inability to compensate for one another functionally. Moreover, these features have facilitated the production of mouse models with robust and predictable phenotypes, and the biophysical/biochemical characterization of individual proteins. The resultant advances demonstrate essential roles for these molecules in building specialized membrane features and facilitating Wnt/β-catenin signaling for angiogenesis. Since tetraspanins are increasingly viewed as potential therapeutic targets, lessons learned from superfamily members with well-documented and essential functions in the retina may prove useful for understanding the roles tetraspanins play in disease more generally.