Differential distributions of novel synaptotagmins: comparison to synapsins

Synaptotagmins and synapsins are prototypical synaptic vesicle proteins that are regulated by Ca2+: Synaptotagmins directly via Ca2+ binding, and synapsins indirectly via phosphorylation by Ca(2+)-dependent protein kinases. Recently, a bewildering multiplicity in the expression of isoforms of these proteins has become apparent. Thus, mammalian brains express at least 8 isoforms of synaptotagmin and 4 isoforms of synapsin if variants arising by differential splicing are included. We have now used in situ hybridization to determine the relative localization of the expression of multiple isoforms of synapsins and synaptotagmins to complement previous studies on their distribution. Our results demonstrate that almost all brain regions co-express all four synapsins at similar levels, suggesting that they are not functionally alternative but complementary. The different isoforms of synaptotagmin exhibit two distinct expression patterns: synaptotagmins that are expressed in a highly differential manner (synaptotagmins I, II and VI), and synaptotagmins with a relatively even distribution of expression similar to synapsins (synaptotagmins III, IV and VII). Our data are consistent with a functional specialization of synaptic vesicle protein isoforms that could result in differential properties of the respective classes of neurons that express them.