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

doi:10.1083/jcb.148.6.1141

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© The Rockefeller University Press, 0021-9525/2000/3/1141/ $5.00
The Journal of Cell Biology, Volume 148, Number 6, March 20, 2000 1141-1150

Brief Report

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

Iñigo Martinez^a, Sabyasachi Chakrabarti^a, Turid Hellevik^b, Jennifer Morehead^a, Kimberly Fowler^a, and Norma W. Andrews^a,b
^a Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
^b Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520

Correspondence to: Norma W. Andrews, Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536. Tel:(203) 737-2410 Fax:(203) 737-2630

Synaptotagmins (Syts) are transmembrane proteins with two Ca²⁺-bindingC₂ domains in their cytosolic region. Syt I, the most widelystudied isoform, has been proposed to function as a Ca²⁺ sensorin synaptic vesicle exocytosis. Several of the twelve knownSyts 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 ubiquitouslyexpressed Syt VII binds syntaxin at free Ca²⁺ concentrations([Ca²⁺]) below 10 µM, whereas other isoforms require 200–500µM [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 theinvolvement of Syt VII in the exocytosis of lysosomes, whichis 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 SytVII is localized on dense lysosomes in normal rat kidney (NRK)fibroblasts, and that GFP-tagged Syt VII is targeted to lysosomesafter transfection. Recombinant fragments containing the C₂Adomain of Syt VII inhibit Ca²⁺-triggered secretion of ß-hexosaminidaseand surface translocation of Lgp120, whereas the C₂A domainof the neuronal- specific isoform, Syt I, has no effect. Antibodiesagainst the Syt VII C₂A domain are also inhibitory in both assays,indicating that Syt VII plays a key role in the regulation ofCa²⁺-dependent lysosome exocytosis.

Key Words: calcium-regulated, calcium sensor, lysosome, secretion, ß-hexosaminidase

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Huynh, K. K., Kay, J. G., Stow, J. L., Grinstein, S. (2007). Fusion, Fission, and Secretion During Phagocytosis. Physiology 22: 366-372 [Abstract] [Full Text]
Osborne, S. L., Wallis, T. P., Jimenez, J. L., Gorman, J. J., Meunier, F. A. (2007). Identification of Secretory Granule Phosphatidylinositol 4,5-Bisphosphate-interacting Proteins Using an Affinity Pulldown Strategy. Mol. Cell. Proteomics 6: 1158-1169 [Abstract] [Full Text]
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Arantes, R. M. E., Andrews, N. W. (2006). A role for synaptotagmin VII-regulated exocytosis of lysosomes in neurite outgrowth from primary sympathetic neurons.. J. Neurosci. 26: 4630-4637 [Abstract] [Full Text]
Tian, J.-H., Wu, Z.-X., Unzicker, M., Lu, L., Cai, Q., Li, C., Schirra, C., Matti, U., Stevens, D., Deng, C., Rettig, J., Sheng, Z.-H. (2005). The Role of Snapin in Neurosecretion: Snapin Knock-Out Mice Exhibit Impaired Calcium-Dependent Exocytosis of Large Dense-Core Vesicles in Chromaffin Cells. J. Neurosci. 25: 10546-10555 [Abstract] [Full Text]
McNeil, A., McNeil, P. L. (2005). Yolk granule tethering: a role in cell resealing and identification of several protein components. J. Cell Sci. 118: 4701-4708 [Abstract] [Full Text]
Steinhardt, R. A. (2005). Shaky Ground for Lysosome-Dependent Membrane Repair. Sci Signal 2005: lc1-lc1 [Abstract] [Full Text]
Andrews, N. W. (2005). Response to "Shaky Ground for Lysosome-Dependent Membrane Repair". Sci Signal 2005: lc2-lc2 [Abstract] [Full Text]
Wang, P., Chicka, M. C., Bhalla, A., Richards, D. A., Chapman, E. R. (2005). Synaptotagmin VII Is Targeted to Secretory Organelles in PC12 Cells, Where It Functions as a High-Affinity Calcium Sensor. Mol. Cell. Biol. 25: 8693-8702 [Abstract] [Full Text]
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Andrews, N. W. (2005). Membrane Resealing: Synaptotagmin VII Keeps Running the Show. Sci Signal 2005: pe19-pe19 [Abstract] [Full Text]
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Atiya-Nasagi, Y., Cohen, H., Medalia, O., Fukudan, M., Sagi-Eisenberg, R. (2005). O-glycosylation is essential for intracellular targeting of synaptotagmins I and II in non-neuronal specialized secretory cells. J. Cell Sci. 118: 1363-1372 [Abstract] [Full Text]
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Fukuda, M., Kanno, E., Satoh, M., Saegusa, C., Yamamoto, A. (2004). Synaptotagmin VII Is Targeted to Dense-core Vesicles and Regulates Their Ca2+-dependent Exocytosis in PC12 Cells. J. Biol. Chem. 279: 52677-52684 [Abstract] [Full Text]
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Fukuda, M., Yamamoto, A. (2004). Effect of Forskolin on Synaptotagmin IV Protein Trafficking in PC12 Cells. J Biochem 136: 245-253 [Abstract] [Full Text]
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Burgoyne, R. D., Morgan, A. (2003). Secretory Granule Exocytosis. Physiol. Rev. 83: 581-632 [Abstract] [Full Text]
Dasgupta, S., Kelly, R. B. (2003). Internalization signals in synaptotagmin VII utilizing two independent pathways are masked by intramolecular inhibitions. J. Cell Sci. 116: 1327-1337 [Abstract] [Full Text]
Jaiswal, J. K., Andrews, N. W., Simon, S. M. (2002). Membrane proximal lysosomes are the major vesicles responsible for calcium-dependent exocytosis in nonsecretory cells. J. Cell Biol. 159: 625-635 [Abstract] [Full Text]
Ramalho-Santos, J., Schatten, G., Moreno, R. D. (2002). Control of Membrane Fusion During Spermiogenesis and the Acrosome Reaction. Biol. Reprod. 67: 1043-1051 [Abstract] [Full Text]
Andrews, N. W. (2002). Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship. J. Cell Biol. 158: 389-394 [Abstract] [Full Text]
Fukuda, M., Katayama, E., Mikoshiba, K. (2002). The Calcium-binding Loops of the Tandem C2 Domains of Synaptotagmin VII Cooperatively Mediate Calcium-dependent Oligomerization. J. Biol. Chem. 277: 29315-29320 [Abstract] [Full Text]
Saegusa, C., Fukuda, M., Mikoshiba, K. (2002). Synaptotagmin V Is Targeted to Dense-core Vesicles That Undergo Calcium-dependent Exocytosis in PC12 Cells. J. Biol. Chem. 277: 24499-24505 [Abstract] [Full Text]
Novak, E. K., Gautam, R., Reddington, M., Collinson, L. M., Copeland, N. G., Jenkins, N. A., McGarry, M. P., Swank, R. T. (2002). The regulation of platelet-dense granules by Rab27a in the ashen mouse, a model of Hermansky-Pudlak and Griscelli syndromes, is granule-specific and dependent on genetic background. Blood 100: 128-135 [Abstract] [Full Text]
Guo, M., Mathieu, P. A., Linebaugh, B., Sloane, B. F., Reiners, J. J. Jr. (2002). Phorbol Ester Activation of a Proteolytic Cascade Capable of Activating Latent Transforming Growth Factor-beta . A PROCESS INITIATED BY THE EXOCYTOSIS OF CATHEPSIN B. J. Biol. Chem. 277: 14829-14837 [Abstract] [Full Text]
Sudhof, T. C. (2002). Synaptotagmins: Why So Many?. J. Biol. Chem. 277: 7629-7632 [Full Text]
McNeil, P. L. (2002). Repairing a torn cell surface: make way, lysosomes to the rescue. J. Cell Sci. 115: 873-879 [Abstract] [Full Text]
Roucard, C., Thomas, C., Pasquier, M.-A., Trowsdale, J., Sotto, J.-J., Neefjes, J., van Ham, M. (2001). In Vivo and In Vitro Modulation of HLA-DM and HLA-DO Is Induced by B Lymphocyte Activation. J. Immunol. 167: 6849-6858 [Abstract] [Full Text]
Caler, E. V., Chakrabarti, S., Fowler, K. T., Rao, S., Andrews, N. W. (2001). The Exocytosis-regulatory Protein Synaptotagmin VII Mediates Cell Invasion by Trypanosoma cruzi. J. Exp. Med. 193: 1097-1104 [Abstract] [Full Text]
Miyake, K., McNeil, P. L., Suzuki, K., Tsunoda, R., Sugai, N. (2001). An actin barrier to resealing. J. Cell Sci. 114: 3487-3494 [Abstract] [Full Text]
Gut, A, Kiraly, C., Fukuda, M, Mikoshiba, K, Wollheim, C., Lang, J (2001). Expression and localisation of synaptotagmin isoforms in endocrine (&bgr;)-cells: their function in insulin exocytosis. J. Cell Sci. 114: 1709-1716 [Abstract]
Caler, E. V., Morty, R. E., Burleigh, B. A., Andrews, N. W. (2000). Dual Role of Signaling Pathways Leading to Ca2+ and Cyclic AMP Elevation in Host Cell Invasion by Trypanosoma cruzi. Infect. Immun. 68: 6602-6610 [Abstract] [Full Text]
Denzer, K, Kleijmeer, M., Heijnen, H., Stoorvogel, W, Geuze, H. (2000). Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci. 113: 3365-3374 [Abstract]
Huang, A. Y., Castle, A. M., Hinton, B. T., Castle, J. D. (2001). Resting (Basal) Secretion of Proteins Is Provided by the Minor Regulated and Constitutive-like Pathways and Not Granule Exocytosis in Parotid Acinar Cells. J. Biol. Chem. 276: 22296-22306 [Abstract] [Full Text]
Fukuda, M., Mikoshiba, K. (2001). Mechanism of the Calcium-dependent Multimerization of Synaptotagmin VII Mediated by Its First and Second C2 Domains. J. Biol. Chem. 276: 27670-27676 [Abstract] [Full Text]
Jarousse, N., Kelly, R. B. (2001). The AP2 binding site of synaptotagmin 1 is not an internalization signal but a regulator of endocytosis. J. Cell Biol. 154: 857-866 [Abstract] [Full Text]