Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo release from Weibel-Palade bodies

• DOI: 10.1083/jcb.201810118
• Publication Date: 2019-05-15T17:45:15Z
• Authors: Katarina T. Miteva; Lucia Pedicini; Lesley A. Wilson; Izzy Jayasinghe; Raphael G. Slip; Katarzyna Marszalek; Hannah J. Gaunt; Fiona Bartoli; Shruthi Deivasiga...; Diego Sobradillo; David J. Beech; Lynn McKeown
• Keywords: Rab; Organelle

Endothelial cells selectively release cargo stored in Weibel-Palade bodies (WPBs) to regulate vascular function, but the underlying mechanisms are poorly understood. Here we show that histamine evokes of proinflammatory ligand, P-selectin, while diverting WPBs carrying non-inflammatory away from plasma membrane microtubule organizing center. This differential trafficking is dependent on Rab46 (CRACR2A), a newly identified Ca2+-sensing GTPase, which localizes subset P-selectin–negative WPBs. After acute stimulation H1 receptor, GTP-bound dynein-dependent retrograde transport along microtubules. Upon continued stimulation, senses localized elevations intracellular calcium and dispersal center–clustered These data demonstrate for first time Rab Rab46, integrates G protein Ca2+ signals couple on-demand selective WPB trafficking.