Ca²⁺ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomes

Synaptotagmin (Syt) VII is a ubiquitously expressed member of the Syt family of Ca²⁺ sensors. It is present on lysosomes in several cell types, where it regulates Ca²⁺-dependent exocytosis. Because [Ca²⁺]_i and exocytosis have been associated with phagocytosis, we investigated the phagocytic ability of macrophages from Syt VII^−/− mice. Syt VII^−/− macrophages phagocytose normally at low particle/cell ratios but show a progressive inhibition in particle uptake under high load conditions. Complementation with Syt VII rescues this phenotype, but only when functional Ca²⁺-binding sites are retained. Reinforcing a role for Syt VII in Ca²⁺-dependent phagocytosis, particle uptake in Syt VII^−/− macrophages is significantly less dependent on [Ca²⁺]_i. Syt VII is concentrated on peripheral domains of lysosomal compartments, from where it is recruited to nascent phagosomes. Syt VII recruitment is rapidly followed by the delivery of Lamp1 to phagosomes, a process that is inhibited in Syt VII^−/− macrophages. Thus, Syt VII regulates the Ca²⁺-dependent mobilization of lysosomes as a supplemental source of membrane during phagocytosis.