title: P-selectin and CD63 use different mechanisms for delivery to Weibel-Palade bodies.
abstract: 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).
authors: MRC Laboratory of Molecular Cell Biology, Cell Biology Unit, University College London, Gower Street, London WC1E 6BT, UK.
authors: Kimberly J
authors: KJ
authors: Harrison-Lavoie
authors: Grégoire
authors: G
authors: Michaux
authors: Lindsay
authors: L
authors: Hewlett
authors: Jasber
authors: J
authors: Kaur
authors: Matthew J
authors: MJ
authors: Hannah
authors: Winnie W Y
authors: WW
authors: Lui-Roberts
authors: Keith E
authors: KE
authors: Norman
authors: Daniel F
authors: DF
authors: Cutler