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

被引:57
作者
Dean, Camin [1 ,2 ]
Dunning, F. Mark [1 ]
Liu, Huisheng [1 ]
Bomba-Warczak, Ewa [1 ]
Martens, Henrik [3 ]
Bharat, Vinita [2 ]
Ahmed, Saheeb [2 ]
Chapman, Edwin R. [1 ]
机构
[1] Univ Wisconsin, Dept Neurosci, Howard Hughes Med Inst, Madison, WI 53706 USA
[2] European Neurosci Inst, D-37077 Gottingen, Germany
[3] Synapt Syst GmbH, D-37079 Gottingen, Germany
基金
美国国家卫生研究院; 欧洲研究理事会;
关键词
HIGH-FREQUENCY STIMULATION; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; NEUROTRANSMITTER RELEASE; HIPPOCAMPAL-NEURONS; CALCIUM SENSOR; SYNAPTIC-TRANSMISSION; TRANSMITTER RELEASE; NEUROTROPHIC FACTOR; MEMBRANE-FUSION;
D O I
10.1091/mbc.E11-08-0707
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1715 / 1727
页数:13
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