期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 22, 页码 4074-4082出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.172510
关键词
Ca2+; Capacitive calcium entry; Ion channel; Junctate; Signal transduction; Membrane contact site; Phagocytosis
类别
资金
- Swiss National Foundation [31003A-149566]
- Swiss National Science Foundation (SNF) [31003A_149566] Funding Source: Swiss National Science Foundation (SNF)
Local intracellular Ca2+ elevations increase the efficiency of phagocytosis, a process that is essential for innate and adaptive immunity. These local Ca2+ elevations are generated in part by the store-operated Ca2+ entry (SOCE) sensor STIM1, which recruits endoplasmic reticulum (ER) cisternae to phagosomes and opens phagosomal Ca2+ channels at ER-phagosome junctions. However, residual ER-phagosome contacts and periphagosomal Ca2+ hotspots remain in Stim1(-/-) cells. Here, we tested whether junctate (also called ASPH isoform 8), a molecule that targets STIM1 to ER-plasma-membrane contacts upon Ca2+-store depletion, cooperates with STIM1 at phagosome junctions. Junctate expression in Stim1(-/-) and Stim1(-/-); Stim2(-/-) phagocytic fibroblasts increased phagocytosis and periphagosomal Ca2+ elevations, yet with only a minimal impact on global SOCE. These Ca2+ hotspots were only marginally reduced by the SOCE channel blocker lanthanum chloride (La3+) but were abrogated by inositol trisphosphate receptor inhibitors 2-APB and xestospongin-C, revealing that unlike STIM1-mediated hotspots, junctate-mediated Ca2+ originates predominantly from periphagosomal Ca2+ stores. Accordingly, junctate accumulates near phagosomes and elongates ER-phagosome junctions in Stim1(-/-) cells. Thus, junctate mediates an alternative mechanism for generating localized Ca2+ elevations within cells, promoting Ca2+ release from internal stores recruited to phagosomes, thereby boosting phagocytosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据