Rab GTPase regulation of phagosome–lysosome fusion is bypassed in the presence of micromolar Ca2+

• DOI: 10.1242/jcs.260806
• Publication Date: 2023-04-19T07:49:35Z
• Authors: Julia Becker; Ariane Schleinitz; Christina Hermsen; Sabrina Rappold; Paul Saftig; Andreas Jeschke; Albert Haas
• Keywords: Rab

Several ATP- and cytosol-dependent fusion processes between membranes of the endocytic exocytic pathways have been biochemically reconstituted. Here, we present a phagosome-lysosome reaction that is driven by micromolar concentrations Ca2+ in absence ATP cytosol. Investigating classical Ca2+-driven (CaFu) side-by-side vitro, using same membrane preparations, show CaFu faster than standard (StaFu), leads to larger products not blocked established inhibitors StaFu. A concentration ∼120 µM supports maximal attachment, 15 fusion, indicating has both membrane-binding activity fusion-promoting activity. StaFu are inhibited mutant form α-SNAP (NAPA) does support soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) activation, mixture cytosolic domains three cognate Q-SNARE proteins, demonstrating role SNAREs merger. independent Ca2+-regulated proteins synaptotagmin-7, calmodulin, annexins A2 A7. We propose corresponds last step when raised from compartment lumen activates for fusion.