CARTOGRAPHY OF NEUREXINS - MORE THAN 1000 ISOFORMS GENERATED BY ALTERNATIVE SPLICING AND EXPRESSED IN DISTINCT SUBSETS OF NEURONS

Neurexins, a family of cell surface proteins specific to brain, are tr anscribed from two promoters in three genes, resulting in three alpha- and three beta-neurexins. In situ hybridization revealed differential but overlapping distributions of neurexin isoforms in different class es of neurons. PCRs demonstrated that alpha-neurexins are alternativel y spliced at five canonical positions, and beta-neurexins at two. Char acterization of many independent bovine neurexin l alpha cDNAs suggest s that different splice sites are used independently. This creates the potential to express more than 1000 distinct neurexin proteins in bra in. The splicing pattern is conserved in rat and cow. Thus, in additio n to somatic gene rearrangements (immunoglobulins and T cell receptors ) and large gene families (odorant receptors), alternative splicing po tentially represents a third mechanism for creating a large number of cell surface receptors that are expressed by specific subsets of cells .