PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
UMass Chan Affiliations
Department of Cell and Developmental BiologyDocument Type
Journal ArticlePublication Date
2015-01-14
Metadata
Show full item recordAbstract
The host endolysosomal compartment is often manipulated by intracellular bacterial pathogens. Salmonella (Salmonella enterica serovar Typhimurium) secrete numerous effector proteins, including SifA, through a specialized type III secretion system to hijack the host endosomal system and generate the Salmonella-containing vacuole (SCV). To form this replicative niche, Salmonella targets the Rab7 GTPase to recruit host membranes through largely unknown mechanisms. We show that Pleckstrin homology domain-containing protein family member 1 (PLEKHM1), a lysosomal adaptor, is targeted by Salmonella through direct interaction with SifA. By binding the PLEKHM1 PH2 domain, Salmonella utilize a complex containing PLEKHM1, Rab7, and the HOPS tethering complex to mobilize phagolysosomal membranes to the SCV. Depletion of PLEKHM1 causes a profound defect in SCV morphology with multiple bacteria accumulating in enlarged structures and significantly dampens Salmonella proliferation in multiple cell types and mice. Thus, PLEKHM1 provides a critical interface between pathogenic infection and the host endolysosomal system.Source
Cell Host Microbe. 2015 Jan 14;17(1):58-71. doi: 10.1016/j.chom.2014.11.011. Link to article on publisher's site.DOI
10.1016/j.chom.2014.11.011Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26456PubMed ID
25500191Notes
Complete author list omitted for brevity. For the full list of authors see article.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.chom.2014.11.011