Fig. 8

Proposed model for tmem33 function in endothelial cells during angiogenesis. When VEGFA binds to its cognate receptor, e.g., Kdrl, the resulting phosphorylation of PLCγ generates inositol 1,4,5-trisphosphate (IP3) and this, in turn, binds to IP3 receptors on the ER membrane, which release Ca²⁺ into the cytosol from intracellular stores. Our data suggest the VEGF-mediated release of Ca²⁺ from ER stores during angiogenesis is dependent on Tmem33 function within the ER membrane. Furthermore, resultant Ca²⁺ oscillations generated in tip cells downstream of Vegfa contribute to phosphorylation of ERK and induction or maintenance of downstream targets including Dll4/Notch signalling, to co-ordinate cellular behaviours during vascular morphogenesis. ER, endoplasmic reticulum; P, plasma membrane