AP-3 adaptor functions in targeting P-selectin to secretory granules in endothelial cells
- PMID: 11389768
- DOI: 10.1034/j.1600-0854.2001.002006406.x
AP-3 adaptor functions in targeting P-selectin to secretory granules in endothelial cells
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 alpha-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.
Similar articles
-
The cytoplasmic domain of P-selectin contains a sorting determinant that mediates rapid degradation in lysosomes.J Cell Biol. 1994 Feb;124(4):435-48. doi: 10.1083/jcb.124.4.435. J Cell Biol. 1994. PMID: 7508941 Free PMC article.
-
Rapid transport of internalized P-selectin to late endosomes and the TGN: roles in regulating cell surface expression and recycling to secretory granules.J Cell Biol. 2000 Oct 2;151(1):107-16. doi: 10.1083/jcb.151.1.107. J Cell Biol. 2000. PMID: 11018057 Free PMC article.
-
P-selectin targeting to secretory lysosomes of Rbl-2H3 cells.J Biol Chem. 2002 Mar 22;277(12):10498-505. doi: 10.1074/jbc.M111293200. Epub 2002 Jan 11. J Biol Chem. 2002. PMID: 11788597
-
A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion.Thromb Haemost. 2001 Jul;86(1):214-21. Thromb Haemost. 2001. PMID: 11487009 Review.
-
Sorting and targeting of melanosomal membrane proteins: signals, pathways, and mechanisms.Pigment Cell Res. 2000 Jun;13(3):128-34. doi: 10.1034/j.1600-0749.2000.130302.x. Pigment Cell Res. 2000. PMID: 10885669 Review.
Cited by
-
An AP-1/clathrin coat plays a novel and essential role in forming the Weibel-Palade bodies of endothelial cells.J Cell Biol. 2005 Aug 15;170(4):627-36. doi: 10.1083/jcb.200503054. Epub 2005 Aug 8. J Cell Biol. 2005. PMID: 16087708 Free PMC article.
-
The adaptor protein AP-3 is required for CD1d-mediated antigen presentation of glycosphingolipids and development of Valpha14i NKT cells.J Exp Med. 2003 Oct 20;198(8):1133-46. doi: 10.1084/jem.20030143. Epub 2003 Oct 13. J Exp Med. 2003. PMID: 14557411 Free PMC article.
-
The Role of Adaptor Proteins in the Biology of Natural Killer T (NKT) Cells.Front Immunol. 2019 Jun 25;10:1449. doi: 10.3389/fimmu.2019.01449. eCollection 2019. Front Immunol. 2019. PMID: 31293596 Free PMC article. Review.
-
Pleiotropic platelet defects in mice with disrupted FOG1-NuRD interaction.Blood. 2011 Dec 1;118(23):6183-91. doi: 10.1182/blood-2011-06-363580. Epub 2011 Oct 11. Blood. 2011. PMID: 21989988 Free PMC article.
-
Sorting nexin 17 accelerates internalization yet retards degradation of P-selectin.Mol Biol Cell. 2004 Jul;15(7):3095-105. doi: 10.1091/mbc.e04-02-0143. Epub 2004 Apr 30. Mol Biol Cell. 2004. PMID: 15121882 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials