P-selectin and CD63 use different mechanisms for delivery to Weibel-Palade bodies

被引:63
作者
Harrison-Lavoie, KJ
Michaux, G
Hewlett, L
Kaur, J
Hannah, MJ
Lui-Roberts, WWY
Norman, KE
Cutler, DF
机构
[1] UCL, Cell Biol Unit, MRC Lab Mol Cell Biol, London WC1E 6BT, England
[2] Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Sheffield S5 7AU, S Yorkshire, England
基金
英国医学研究理事会;
关键词
AP-3; CD63; LRO; P-selectin; secretory granules; von Willebrand factor;
D O I
10.1111/j.1600-0854.2006.00415.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The biogenesis of endothelial-specific Weibel-Palade bodies (WPB) is poorly understood, despite their key role in both haemostasis and inflammation. Biogenesis of specialized organelles of haemopoietic cells is often adaptor protein complex 3-dependent (AP-3-dependent), and AP-3 has previously been shown to play a role in the trafficking of both WPB membrane proteins, P-selectin and CD63. However, WPB are thought to form at the trans Golgi network (TGN), which is inconsistent with a role for AP-3, which operates in post-Golgi trafficking. We have therefore investigated in detail the mechanisms of delivery of these two membrane proteins to WPB. We find that P-selectin is recruited to forming WPB in the trans-Golgi by AP-3-independent mechanisms that use sorting information within both the cytoplasmic tail and the lumenal domain of the receptor. In contrast, CD63 is recruited to already-budded WPB by an AP-3-dependent route. These different mechanisms of recruitment lead to the presence of distinct immature and mature populations of WPB in human umbilical vein endothelial cells (HUVEC).
引用
收藏
页码:647 / 662
页数:16
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