A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium
A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium
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DOI：
10.1083/jcb.200611056
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发表时间：
2007-01-29
影响因子：
7.8
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
Smith, Adam C.;Do Heo, Won;Brumell, John H.
Rab鸟苷三磷酸酶（GTdR）家族的成员是膜运输的关键调节剂。在这里，我们研究了48只家兔与模型吞噬体的关系，该模型吞噬体含有一种非侵入性的沙门氏菌鼠伤寒血清型突变体（S。鼠伤寒沙门氏菌）。这种突变体运输到溶酶体，并使我们能够确定哪些Rab定位于成熟的吞噬体。总共有18只兔子与成熟的吞噬体相关，每一种都有自己的关联动力学。Rab 23和Rab 35的显性负突变体抑制吞噬体-溶酶体融合。大量的Rab GTP酶定位于野生型沙门氏菌含有的空泡（SCV），其不与溶酶体融合。然而，一些Rab（8B、13、23、32和35）被排除在野生型SCV之外，而其他Rab（5A、5 B、5C、7A、11 A和11B）在该区室上富集。我们的研究表明，一个复杂的Rab GTP酶网络控制着向溶酶体的内吞过程，这是由S。鼠伤寒沙门氏菌，使其细胞内生长。
Members of the Rab guanosine triphosphatase ( GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium ( S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome- lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella- containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth.