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Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 1992 Mar; Vol. 3 (3), pp. 309-21. - Publication Year :
- 1992
-
Abstract
- P-selectin (CD62), formerly called GMP-140 or PADGEM, is a membrane protein located in secretory storage granules of platelets and endothelial cells. To study the mechanisms responsible for the targeting of P-selectin 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 redirected 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.
- Subjects :
- Adrenocorticotropic Hormone metabolism
Animals
Cells, Cultured
Fluorescent Antibody Technique
Immunohistochemistry
Mice
P-Selectin
Platelet Membrane Glycoproteins genetics
Platelet Membrane Glycoproteins isolation & purification
Protein Sorting Signals genetics
Transfection genetics
Cytoplasmic Granules metabolism
Platelet Membrane Glycoproteins metabolism
Protein Sorting Signals metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1059-1524
- Volume :
- 3
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 1378326
- Full Text :
- https://doi.org/10.1091/mbc.3.3.309