Imperial College London
Alternate

ProfessorVaniaBraga

Faculty of Medicine, National Heart & Lung Institute

Professor of Cellular Signalling
 
 
 
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Contact

 

+44 (0)20 7594 3233v.braga

 
 
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Location

 

Office no. 105Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jaber:2016:10.1242/jcs.192260,
author = {Jaber, N and Mohd-Naim, N and Wang, Z and DeLeon, JL and Kim, S and Zhong, H and Sheshadri, N and Dou, Z and Edinger, AL and Du, G and Braga, VMM and Zong, W-X},
doi = {10.1242/jcs.192260},
journal = {JOURNAL OF CELL SCIENCE},
pages = {4424--4435},
title = {Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus},
url = {http://dx.doi.org/10.1242/jcs.192260},
volume = {129},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The class III phosphoinositide 3-kinase (PI3K) Vps34 (also known as PIK3C3 in mammals) produces phosphatidylinositol 3-phosphate [PI(3)P] on both early and late endosome membranes to control membrane dynamics. We used Vps34-deficient cells to delineate whether Vps34 has additional roles in endocytic trafficking. In Vps34−/− mouse embryonic fibroblasts (MEFs), transferrin recycling and EEA1 membrane localization were unaffected despite elevated Rab5-GTP levels. Strikingly, a large increase in Rab7-GTP levels, an accumulation of enlarged late endosomes, and decreased EGFR degradation were observed in Vps34-deficient cells. The hyperactivation of Rab7 in Vps34-deficient cells stemmed from the failure to recruit the Rab7 GTPase-activating protein (GAP) Armus (also known as TBC1D2), which binds to PI(3)P, to late endosomes. Protein–lipid overlay and liposome-binding assays reveal that the putative pleckstrin homology (PH) domain in Armus can directly bind to PI(3)P. Elevated Rab7-GTP led to the failure of intraluminal vesicle (ILV) formation and lysosomal maturation. Rab7 silencing and Armus overexpression alleviated the vacuolization seen in Vps34-deficient cells. Taken together, these results demonstrate that Vps34 has a previously unknown role in regulating Rab7 activity and late endosomal trafficking.
AU  - Jaber,N
AU  - Mohd-Naim,N
AU  - Wang,Z
AU  - DeLeon,JL
AU  - Kim,S
AU  - Zhong,H
AU  - Sheshadri,N
AU  - Dou,Z
AU  - Edinger,AL
AU  - Du,G
AU  - Braga,VMM
AU  - Zong,W-X
DO  - 10.1242/jcs.192260
EP  - 4435
PY  - 2016///
SN  - 0021-9533
SP  - 4424
TI  - Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus
T2  - JOURNAL OF CELL SCIENCE
UR  - http://dx.doi.org/10.1242/jcs.192260
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000391102600011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/59131
VL  - 129
ER  -
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