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