Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway

Magali Disdier, James H. Morrissey, Robert D. Fugate, Dorothy F. Bainton, Rodger P. McEver

Research output: Contribution to journalArticlepeer-review

Abstract

P-selectin (CD62), formerly called GMP-140 or PADGEM, is a membrane protein located in secretory granules of platelets and endothelial cells. To study the mechanisms responsible for the targeting of P-selection to storage granules, we transfected its cDNA into COS-7 and CHO-K1 cells, which lack a regulated exocytic pathway, or into AtT20 cells, which are capable of regulated secretion. P-selectin was expressed on the plasma membrane of COS-7 and CHO-K1 cells but was concentrated in storage granules of AtT20 cells. Immunogold electron microscopy indicated that the electron-dense granules containing P-selectin in AtT20 cells also stored the endogenous soluble hormone ACTH. Activation of AtT20 cells with 8-Br-cAmp increased the surface expression of P-selectin, consistent with agonist-induced fusion of granule membranes with the plasma membrane. Deletion of the last 23 amino acids of the 35-residue cytoplasmic domain resulted in delivery of P-selectin to the plasma membrane of AtT20 cells. Replacement of the cytoplasmic tail of tissue factor, a plasma membrane protein, with the cytoplasmic domain of P-selectin re-directed the chimeric molecule to granules. We conclude that the cytoplasmic domain of P-selectin is both necessary and sufficient for sorting of membrane proteins into the regulated pathway of secretion.

Original languageEnglish (US)
Pages (from-to)309-321
Number of pages13
JournalMolecular biology of the cell
Volume3
Issue number3
DOIs
StatePublished - Mar 1992
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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