TROPOMYOSIN ISOFORM DIVERSITY AND NEURONAL MORPHOGENESIS

Tropomyosins (Tm) are a large family of isoforms obtained from multipl e genes and by extensive alternative splicing. They bind in the alpha- helical groove of the actin filament and are therefore core components of this extensive cytoskeletal system. In non-muscle cells the Tm iso forms have been implicated in a diversity of processes including cytok inesis, vesicle transport, motility, morphogenesis and cell transforma tion. Using immunohistochemical localization in cultured primary corti cal neurons with an antibody that potentially identifies all non-muscl e TM5 gene isoforms compared with one that specifically identifies a s ubset of isoforms, the possibility was raised that there were consider ably more isoforms derived from this gene than the four previously des cribed. Using polymerase chain reaction (PCR) analysis we have now sho wn that the rat brain generates at least 10 mRNA isoforms using multip le combinations of terminal exons and two internal exons. There is ext ensive developmental regulation of these isoforms in the brain and the re appears to be a switch in the preferential use of the two internal exons 6a to 6b from the embryonic to the adult isoforms. Specific isof orms using alternate carboxyl-terminal exons are differentially locali zed within the adult rat cerebellum. It is suggested that the tightly regulated spatial and temporal expression of Tm isoforms plays an impo rtant role in the development and maintenance of specific neuronal com partments. This may be acheived by isoforms providing unique structura l properties to actin-based filaments within functionally distinct neu ronal domains.