AP-3 adaptor functions in targeting P-selectin to secretory granules in endothelial cells

被引:21
作者
Daugherty, BL
Straley, KS
Sanders, JM
Phillips, JW
Disdier, M
McEver, RP
Green, SA
机构
[1] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA
[2] Univ Virginia, Sch Med, Dept Med, Div Cardiovasc, Charlottesville, VA 22908 USA
[3] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, WK Warren Med Res Inst, Oklahoma City, OK 73104 USA
[4] Univ Oklahoma, Hlth Sci Ctr, Dept Med, WK Warren Med Res Inst, Oklahoma City, OK 73104 USA
[5] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA
关键词
adaptor; alpha-granule; platelets; P-selectin; secretory granule; sorting; Weibel-Palade body;
D O I
10.1034/j.1600-0854.2001.002006406.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 enclothelial 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.
引用
收藏
页码:406 / 413
页数:8
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