A: An overview of PI(P) synthesis in endolysosomes. PI(3)P is synthesized from PI via a PI 3-kinase (Vps34) present in endosomes, while PI(3,5)P2 is synthesized from PI(3)P via a PI 5-kinase (PIKfyve/Fab1). PIKfyve is a PI(3)P effector that is associated with late endosomes and lysosomes (LELs), and is positively regulated by Vac14. PI(3,5)P2 can be dephosphorylated by Fig4 or MTM/MTMRs to generate PI(3)P or PI5P, respectively.
B: The distribution of PI(3)P and PI(3,5)P2 associated with the membranes of early and late endosomes, as well as lysosomes, are represented by yellow and red outlines at the membrane of these vesicle types. respectively [35]. TRPML1–3, TRPM2, and TPC1–2 are putative Ca2+ release channels associated with endolysosomal membranes that are also labeled in this diagram [69,75,76]. TRPML1–3 channels are predominantly localized to LELs, while TRPML2 and TRPML3 are also associated with recycling and early endosomes, respectively. TPC2 is mainly localized in the LELs, and TPC1 is mainly associated with early and late endosomes. TRPM2 is expressed in specific cell types, and is associated with LELs as well as the plasma membrane. The concentration of Ca2+ stores associated with each vesicle type is also indicated, with luminal [Ca2+] estimated to be in the micro- to millimolar ranges.