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AP-3 Adaptor Functions in Targeting P-Selectin to Secretory Granules in Endothelial Cells.
- Source :
-
Traffic . Jun2001, Vol. 2 Issue 6, p406-413. 8p. 7 Diagrams. - Publication Year :
- 2001
-
Abstract
- P-selectin, a cell adhesion protein participating in the early stages of inflammation, contains multiple sorting signals that regulate its cell surface expression. Targeting to secretory granules regulates delivery of P-selectin to the cell surface. Internalization followed by sorting from early to late endosomes mediates rapid removal of P-selectin from the surface. We show here that the P-selectin cytoplasmic domain bound AP-2 and AP-3 adaptor complexes in vitro. The amino acid substitution L768A, which abolishes endosomal sorting and impairs granule targeting of P-selectin, reduced binding of AP-3 adaptors but not AP-2 adaptors. Turnover of P-selectin was 2.4-fold faster than turnover of transferrin receptor in AP-3-deficient mocha fibroblasts, similar to turnover of these two proteins in AP-3-competent cells, demonstrating that AP-3 function is not required for endosomal sorting. However, sorting P-selectin to secretory granules was defective in endothelial cells from AP-3-deficient pearl mice, demonstrating a role for AP-3 adaptors in granule assembly in endothelial cells. P-selectin sorting to platelet α-granules was normal in pearl mice, consistent with earlier evidence that granule targeting of P-selectin is mechanistically distinct in endothelial cells and platelets. These observations establish that AP-3 adaptor functions in assembly of conventional secretory granules, in addition to lysosomes and the ‘lysosome-like’ secretory granules of platelets and melanocytes. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CELL adhesion molecules
*PROTEINS
*ALKALINE phosphatase
*ENDOTHELIUM
*PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 13989219
- Volume :
- 2
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Traffic
- Publication Type :
- Academic Journal
- Accession number :
- 4593932
- Full Text :
- https://doi.org/10.1034/j.1600-0854.2001.002006406.x