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Molecular and Cellular Biology, October 2005, p. 8693-8702, Vol. 25, No. 19
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.19.8693-8702.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Synaptotagmin VII Is Targeted to Secretory Organelles in PC12 Cells, Where It Functions as a High-Affinity Calcium Sensor{dagger}

Ping Wang, Michael C. Chicka, Akhil Bhalla, David A. Richards, and Edwin R. Chapman*

Department of Physiology, University of Wisconsin, Madison, Wisconsin

Received 6 May 2005/ Returned for modification 27 June 2005/ Accepted 8 July 2005

Synaptotagmin (syt) I is thought to act as a Ca2+ sensor that regulates neuronal exocytosis. Fifteen additional isoforms of syt have been identified, but their functions are less well understood. Here, we used PC12 cells to test the idea that different isoforms of syt impart cells with distinct metal (i.e., Ca2+, Ba2+, and Sr2+) requirements for secretion. These cells express syt's I and IX (syt IX sometimes referred to as syt V), which have low apparent metal affinities, at much higher levels than syt VII, which we show has a relatively high apparent affinity for metals. We found that syt I and VII partially colocalize on large dense core vesicles and that upregulation of syt VII produces a concomitant increase in the divalent cation sensitivity of catecholamine release from PC12 cells. Furthermore, RNA interference-mediated knockdown of endogenous syt VII reduced the metal sensitivity of release. These data support the hypothesis that the complement of syt's expressed by a cell, in conjunction with their metal affinity, determines the divalent cation sensitivity of exocytosis.

* Corresponding author. Mailing address: Department of Physiology, University of Wisconsin, 1300 University Ave., SMI 129, Madison, WI 53706. Phone: (608) 263-1762. Fax: (608) 265-5512. E-mail: chapman{at}physiology.wisc.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, October 2005, p. 8693-8702, Vol. 25, No. 19
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.19.8693-8702.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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