Access

You are not currently logged in.

Access JSTOR through your library or other institution:

login

Log in through your institution.

Synaptotagmin VII Regulates Ca2+-Dependent Exocytosis of Lysosomes in Fibroblasts

Iñigo Martinez, Sabyasachi Chakrabarti, Turid Hellevik, Jennifer Morehead, Kimberly Fowler and Norma W. Andrews
The Journal of Cell Biology
Vol. 148, No. 6 (Mar. 20, 2000), pp. 1141-1149
Stable URL: http://www.jstor.org/stable/1619719
Page Count: 9
  • More info
  • Cite this Item
Synaptotagmin VII Regulates  Ca2+-Dependent Exocytosis of Lysosomes in Fibroblasts
Preview not available

Abstract

Synaptotagmins (Syts) are transmembrane proteins with two Ca2+-binding C2 domains in their cytosolic region. Syt I, the most widely studied isoform, has been proposed to function as a Ca2+ sensor in synaptic vesicle exocytosis. Several of the twelve known Syts are expressed primarily in brain, while a few are ubiquitous (Sudhof, T.C., and J. Rizo. 1996. Neuron. 17:379-388; Butz, S., R. Fernandez-Chacon, F. Schmitz, R. Jahn, and T.C. Sudhof. 1999. J. Biol. Chem. 274:18290-18296). The ubiquitously expressed Syt VII binds syntaxin at free Ca2+ concentrations ([ Ca2+]) below 10 μM, whereas other isoforms require 200-500 μM [ Ca2+] or show no Ca2+-dependent syntaxin binding (Li, C., B. Ullrich, Z. Zhang, R.G.W. Anderson, N. Brose, and T.C. Sudhof. 1995. Nature. 375:594-599). We investigated the involvement of Syt VII in the exocytosis of lysosomes, which is triggered in several cell types at 1-5 μM [ Ca2+] (Rodríguez, A., P. Webster, J. Ortego, and N.W. Andrews. 1997. J. Cell Biol. 137:93-104). Here, we show that Syt VII is localized on dense lysosomes in normal rat kidney (NRK) fibroblasts, and that GFP-tagged Syt VII is targeted to lysosomes after transfection. Recombinant fragments containing the C2 A domain of Syt VII inhibit Ca2+-triggered secretion of β-hexosaminidase and surface translocation of Lgp120, whereas the C2 A domain of the neuronal-specific isoform, Syt I, has no effect. Antibodies against the Syt VII C2 A domain are also inhibitory in both assays, indicating that Syt VII plays a key role in the regulation of Ca2+-dependent lysosome exocytosis.

Page Thumbnails

  • Thumbnail: Page 
1141
    1141
  • Thumbnail: Page 
1142
    1142
  • Thumbnail: Page 
1143
    1143
  • Thumbnail: Page 
1144
    1144
  • Thumbnail: Page 
1145
    1145
  • Thumbnail: Page 
1146
    1146
  • Thumbnail: Page 
1147
    1147
  • Thumbnail: Page 
1148
    1148
  • Thumbnail: Page 
1149
    1149