Cysteine string protein (CSP) is an insulin secretory granule-associated protein regulating β-cell exocytosis

Hilary Brown, Olof Larsson, Robert Bränström, Shao Nian Yang, Barbara Leibiger, Ingo Leibiger, Gabriel Fried, Tilo Moede, Jude T. Deeney, Graham R. Brown, Gunilla Jacobsson, Christopher J. Rhodes, Janice E.A. Braun, Richard H. Scheller, Barbara E. Corkey, Per Olof Berggren, Björn Meister

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Cysteine string proteins (CSPs) are novel synaptic vesicle-associated protein components characterized by an N-terminal J-domain and a central palmitoylated string of cysteine residues. The cellular localization and functional role of CSP was studied in pancreatic endocrine cells. In situ hybridization and RT-PCR analysis demonstrated CSP mRNA expression in insulin-producing cells. CSP1 mRNA was present in pancreatic islets; both CSP1 and CSP2 mRNAs were seen in insulin-secreting cell lines. Punctate CSP-like immunoreactivity (CSP-LI) was demonstrated in most islets of Langerhans cells, acinar cells and nerve fibers of the rat pancreas. Ultrastructural analysis showed CSP-LI in close association with membranes of secretory granules of cells in the endo- and exocrine pancreas. Subcellular fractionation of insulinoma cells showed CSP1 (34/36 kDa) in granular fractions; the membrane and cytosol fractions contained predominantly CSP2 (27 kDa). The fractions also contained proteins of 72 and 70 kDa, presumably CSP dimers. CSP1 overexpression in INS-1 cells or intracellular administration of CSP antibodies into mouse ob/ob β-cells did not affect voltage-dependent Ca2+-channel activity. Amperometric measurements showed a significant decrease in insulin exocytosis in individual INS-1 cells after CSP1 overexpression. We conclude that CSP is associated with insulin secretory granules and that CSP participates in the molecular regulation of insulin exocytosis by mechanisms not involving changes in the activity of voltage-gated Ca2+-channels.

Original languageEnglish (US)
Pages (from-to)5048-5058
Number of pages11
JournalEMBO Journal
Volume17
Issue number17
DOIs
StatePublished - Sep 1 1998

Keywords

  • Calcium
  • Chaperone
  • Heat shock protein
  • Pancreas
  • Secretion

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Cysteine string protein (CSP) is an insulin secretory granule-associated protein regulating β-cell exocytosis'. Together they form a unique fingerprint.

Cite this