Junctate boosts phagocytosis by recruiting endoplasmic reticulum Ca2+ stores near phagosomes.
J Cell Sci
; 128(22): 4074-82, 2015 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-26446257
ABSTRACT
Local intracellular Ca(2+) elevations increase the efficiency of phagocytosis, a process that is essential for innate and adaptive immunity. These local Ca(2+) elevations are generated in part by the store-operated Ca(2+) entry (SOCE) sensor STIM1, which recruits endoplasmic reticulum (ER) cisternae to phagosomes and opens phagosomal Ca(2+) channels at ER-phagosome junctions. However, residual ER-phagosome contacts and periphagosomal Ca(2+) 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 Ca(2+)-store depletion, cooperates with STIM1 at phagosome junctions. Junctate expression in Stim1(-/-) and Stim1(-/-); Stim2(-/-) phagocytic fibroblasts increased phagocytosis and periphagosomal Ca(2+) elevations, yet with only a minimal impact on global SOCE. These Ca(2+) hotspots were only marginally reduced by the SOCE channel blocker lanthanum chloride (La(3+)) but were abrogated by inositol trisphosphate receptor inhibitors 2-APB and xestospongin-C, revealing that unlike STIM1-mediated hotspots, junctate-mediated Ca(2+) originates predominantly from periphagosomal Ca(2+) stores. Accordingly, junctate accumulates near phagosomes and elongates ER-phagosome junctions in Stim1(-/-) cells. Thus, junctate mediates an alternative mechanism for generating localized Ca(2+) elevations within cells, promoting Ca(2+) release from internal stores recruited to phagosomes, thereby boosting phagocytosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
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Fagossomos
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Proteínas de Ligação ao Cálcio
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Cálcio
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Retículo Endoplasmático
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Oxigenases de Função Mista
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Proteínas de Membrana
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Proteínas Musculares
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
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