Axonal and dendritic synaptotagmin isoforms revealed by a pHluorin-syt functional screen

Department of Neuroscience, Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA.
Molecular biology of the cell (Impact Factor: 4.47). 03/2012; 23(9):1715-27. DOI: 10.1091/mbc.E11-08-0707
Source: PubMed


The synaptotagmins (syts) are a family of molecules that regulate membrane fusion. There are 17 mammalian syt isoforms, most of which are expressed in the brain. However, little is known regarding the subcellular location and function of the majority of these syts in neurons, largely due to a lack of isoform-specific antibodies. Here we generated pHluorin-syt constructs harboring a luminal domain pH sensor, which reports localization, pH of organelles to which syts are targeted, and the kinetics and sites of exocytosis and endocytosis. Of interest, only syt-1 and 2 are targeted to synaptic vesicles, whereas other isoforms selectively recycle in dendrites (syt-3 and 11), axons (syt-5, 7, 10, and 17), or both axons and dendrites (syt-4, 6, 9, and 12), where they undergo exocytosis and endocytosis with distinctive kinetics. Hence most syt isoforms localize to distinct secretory organelles in both axons and dendrites and may regulate neuropeptide/neurotrophin release to modulate neuronal function.

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    • "Clearly, syt 7 is not selectively targeted to the plasma membrane (though, again, like all syt isoforms, some fraction is present in the plasma membrane [Dean et al., 2012a]). Moreover, pHluorinsyt 7 does not recycle with SV-like kinetics, even after repetitive stimulation (Dean et al., 2012a), excluding the possibility that syt 7 traffics to SVs before, during, or after stimulation. So, syt 7 is likely to regulate replenishment either from the plasma membrane, or from LDCVs or lysosomes. "
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