We are interested in the role of the P2X4 purinergic receptor in lysosome physiology and Ca²⁺ signalling. These widely expressed receptors are targeted to endolysosomes where they mediate the release of Ca²⁺ in a manner dependent on luminal ATP and pH. Recently our interest has focused on the regulation of these receptors and their role in breast cancer progression.  Lysosomal P2X4 receptors are activated downstream of Ca²⁺ signals evoked by plasma membrane P2X7 and H1-histamine receptors. These signals promote lysosome alkalinization which leads to an exaggerated rise in Ca²⁺. This novel form of Ca²⁺-induced Ca²⁺ release regulates lysosome trafficking and fusion. Lysosome fusion with the plasma membrane and release of cathepsins enhances breast cancer cell invasiveness and metastases.

References:
Cao Q, Zhong XZ, Zou Y, Murrell-Lagnado R, Zhu MX, Dong XP (2015) Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion.  J Cell Biol 209: 879-94.
   
Srivats S, Balasuriya D, Pasche M, Vistal G, Edwardson JM, Taylor CW, Murrell-Lagnado RD (2016)  Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1.
J Cell Biol 213: 65-79.