Synaptotagmin VII as a Plasma Membrane Ca super(2+) Sensor in Exocytosis

• Published in: Neuron (Cambridge, Mass.) Vol. 30; no. 2; pp. 459 - 473
• Main Authors: Sugita, S, Han, Weiping, Butz, S, Liu, Xinran, Fernandez-Chacon, R, Lao, Ye, Suedhof, T C
• Format: Journal Article
• Language: English
• Published: 01.05.2001
• ISSN: 0896-6273

Synaptotagmins I and II are Ca super(2+) binding proteins of synaptic vesicles essential for fast Ca super(2+)-triggered neurotransmitter release. However, central synapses and neuroendocrine cells lacking these synaptotagmins still exhibit Ca super(2+)-evoked exocytosis. We now propose that synaptotagmin VII functions as a plasma membrane Ca super(2+) sensor in synaptic exocytosis complementary to vesicular synaptotagmins. We show that alternatively spliced forms of synaptotagmin VII are expressed in a developmentally regulated pattern in brain and are concentrated in presynaptic active zones of central synapses. In neuroendocrine PC12 cells, the C sub(2)A and C sub(2)B domains of synaptotagmin VII are potent inhibitors of Ca super(2+)-dependent exocytosis, but only when they bind Ca super(2+). Our data suggest that in synaptic vesicle exocytosis, distinct synaptotagmins function as independent Ca super(2+) sensors on the two fusion partners, the plasma membrane (synaptotagmin VII) versus synaptic vesicles (synaptotagmins I and II).