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

Molecular Biology of the Cell - Tập 23 Số 9 - Trang 1715-1727 - 2012
Camin Dean1,2, F. Mark Dunning1, Huisheng Liu1, Ewa Bomba-Warczak1, Henrik Martens3, Vinita Bharat2, Saheeb Ahmed2, Edwin R. Chapman1
1Department of Neuroscience, Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706
2European Neuroscience Institute, 37077 Göttingen, Germany
3Synaptic Systems GmbH, 37079 Göttingen, Germany

Tóm tắt

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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Molecular Biology of the Cell

Tập 23 Số 9

1715-1727

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