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.

译文

Synaptotagmin (Syt) VII是Ca2 + 传感器Syt家族中普遍表达的成员。它存在于几种细胞类型的溶酶体上,在其中调节Ca2依赖性胞吐作用。由于 [Ca2] i和胞吐作用与吞噬作用有关,因此我们研究了Syt VII-/-小鼠巨噬细胞的吞噬能力。Syt VII-/-巨噬细胞通常在低颗粒/细胞比率下吞噬,但在高负荷条件下显示出对颗粒吸收的逐渐抑制。与Syt VII的互补可以挽救这种表型,但只有在保留功能性Ca2结合位点的情况下。增强Syt VII在Ca2依赖性吞噬作用中的作用,Syt VII-/-巨噬细胞中的颗粒摄取对 [Ca2] i的依赖性明显降低。Syt VII集中在溶酶体区室的外围结构域上,从那里募集到新生的吞噬体。Syt VII募集后迅速将Lamp1递送到吞噬体,这一过程在Syt VII-/-巨噬细胞中受到抑制。因此,Syt VII调节溶酶体的Ca2依赖性动员,作为吞噬作用期间膜的补充来源。

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