Synaptotagmins and cell-to-cell communication at neuronal synapse
 
Bazbek Davletov
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
*email: baz@mrc-lmb.cam.ac.uk
 
Intracellular membrane traffic is governed by a conserved set of proteins including SNARE fusion proteins and synaptotagmins (Syts). The mammalian Syt family consist of 16 isoforms. Syts are membrane proteins that possess tandem C2 domains (C2AB) implicated in calcium-dependent phospholipid binding. We performed a pair-wise amino acid sequence comparison together with functional studies of rat Syt C2ABs to examine common and divergent properties within the mammalian family. Sequence analysis indicates three different C2AB classes, the members of which share a high degree of sequence similarity.  All the other C2ABs are highly divergent in sequence. Interestingly, nearly half of the Syt family does not exhibit calcium-dependent phospholipid binding. Syts do however possess a more conserved function, namely constitutive binding to target SNARE heterodimers. All tested isoforms bound the target SNARE dimer composed of syntaxin1 and SNAP-25. Our study suggests that both calcium-sensitive and insensitive Syt isoforms function in membrane traffic to interact with the target SNARE heterodimer on the pathway to membrane fusion.
 
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