The full-of-bacteria gene is required for phagosome maturation during immune defense in Drosophila.
The full-of-bacteria gene is required for phagosome maturation during immune defense in Drosophila.
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DOI：
10.1083/jcb.201008119
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发表时间：
2011-02-07
期刊：
影响因子：
--
通讯作者：
Krämer H
中科院分区：
文献类型：
--
作者：
Akbar MA;Tracy C;Kahr WH;Krämer H
果蝇fob编码Vps16跳复合体亚基的同源物，吞噬体成熟和消化吞噬病原体所需的亚基。关节紊乱、肾功能障碍和胆汁淤积症(ARC)综合征是一种由VPS33B或VPS16B基因突变引起的致命隐性疾病。两者都编码酵母中液泡融合所需的啤酒花复合体的Vps33p和Vps16p亚基的同源物。在这里，我们描述了编码果蝇Vps16B的完整细菌(Fob)基因的突变。离岸价为零的果蝇是纯合的、有活力的和有生育能力的。然而，它们的免疫防御存在缺陷，使它们对非致病细菌的感染高度敏感。FOB血细胞(苍蝇巨噬细胞)吞噬细菌，但不能消化它们。吞噬小体经历了成熟的早期阶段，并过渡到Rab7阳性阶段，但不成熟到完全酸化的吞噬小体。这反映了FOB在吞噬小体与晚期内噬菌体/溶酶体融合中的特殊要求。相反，自噬小体和内小体的货物在FOB细胞中表现出正常的溶酶体递送。这些发现表明，吞噬小体成熟缺陷可能导致ARC患者的症状，包括反复感染。
Drosophila fob encodes a homolog of the Vps16 HOPS complex subunit, required for phagosome maturation and digestion of engulfed pathogens. Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a fatal recessive disorder caused by mutations in the VPS33B or VPS16B genes. Both encode homologues of the Vps33p and Vps16p subunits of the HOPS complex necessary for fusions of vacuoles in yeast. Here, we describe a mutation in the full-of-bacteria (fob) gene, which encodes Drosophila Vps16B. Flies null for fob are homozygous viable and fertile. They exhibit, however, a defect in their immune defense that renders them hypersensitive to infections with nonpathogenic bacteria. fob hemocytes (fly macrophages) engulf bacteria but fail to digest them. Phagosomes undergo early steps of maturation and transition to a Rab7-positive stage, but do not mature to fully acidified phagolysosomes. This reflects a specific requirement of fob in the fusion of phagosomes with late endosomes/lysosomes. In contrast, cargo of autophagosomes as well as endosomes exhibit normal lysosomal delivery in fob cells. These findings suggest that defects in phagosome maturation may contribute to symptoms of ARC patients including recurring infections.
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DOI：
10.1083/jcb.124.5.677
发表时间：
1994-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Desjardins M;Huber LA;Parton RG;Griffiths G
通讯作者：
Griffiths G
影响因子：
30.8
作者：
Cullinane AR;Straatman-Iwanowska A;Zaucker A;Wakabayashi Y;Bruce CK;Luo G;Rahman F;Gürakan F;Utine E;Ozkan TB;Denecke J;Vukovic J;Di Rocco M;Mandel H;Cangul H;Matthews RP;Thomas SG;Rappoport JZ;Arias IM;Wolburg H;Knisely AS;Kelly DA;Müller F;Maher ER;Gissen P
通讯作者：
Gissen P
影响因子：
30.8
作者：
Gissen, P;Johnson, CA;Maher, ER
通讯作者：
Maher, ER
DOI：
10.1073/pnas.0535280100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Gong, WJ;Golic, KG
通讯作者：
Golic, KG
影响因子：
64.5
作者：
Poteryaev, Dmitry;Datta, Sunando;Spang, Anne
通讯作者：
Spang, Anne