TY - JOUR
T1 - TBC1D16 is a Rab4A GTPase activating protein that regulates receptor recycling and EGF receptor signaling
AU - Goueli, Basem S.
AU - Powell, Marianne Broome
AU - Finger, Elizabeth C.
AU - Pfeffer, Suzanne R.
PY - 2012/9/25
Y1 - 2012/9/25
N2 - Rab4A is a master regulator of receptor recycling from endocytic compartments to the plasmamembrane. The protein TBC1D16 is upregulated in melanoma, and TBC1D16-overexpressing melanoma cells are dependent on TBC1D16. We show here that TBC1D16 enhances the intrinsic rate of GTP hydrolysis by Rab4A. TBC1D16 is both cytosolic and membrane associated; the membrane-associated pool colocalizes with transferrin and EGF receptors (EGFRs) and early endosome antigen 1, but not with LAMP1 protein. Expression of two TBC1D16 isoforms, but not the inactive R494A mutant, reduces transferrin receptor recycling but has no effect on transferrin receptor internalization. Expression of TBC1D16 alters GFPRab4A membrane localization. In HeLa cells, overexpression of TBC1D16 enhances EGF-stimulated EGFR degradation, concomitant with decreasedEGFRlevels andsignaling. Thus,TBC1D16is a GTPase activating protein for Rab4A that regulates transferrin receptor recycling and EGFR trafficking and signaling.
AB - Rab4A is a master regulator of receptor recycling from endocytic compartments to the plasmamembrane. The protein TBC1D16 is upregulated in melanoma, and TBC1D16-overexpressing melanoma cells are dependent on TBC1D16. We show here that TBC1D16 enhances the intrinsic rate of GTP hydrolysis by Rab4A. TBC1D16 is both cytosolic and membrane associated; the membrane-associated pool colocalizes with transferrin and EGF receptors (EGFRs) and early endosome antigen 1, but not with LAMP1 protein. Expression of two TBC1D16 isoforms, but not the inactive R494A mutant, reduces transferrin receptor recycling but has no effect on transferrin receptor internalization. Expression of TBC1D16 alters GFPRab4A membrane localization. In HeLa cells, overexpression of TBC1D16 enhances EGF-stimulated EGFR degradation, concomitant with decreasedEGFRlevels andsignaling. Thus,TBC1D16is a GTPase activating protein for Rab4A that regulates transferrin receptor recycling and EGFR trafficking and signaling.
KW - Endocytosis
KW - Membrane traffic
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U2 - 10.1073/pnas.1204540109
DO - 10.1073/pnas.1204540109
M3 - Article
C2 - 23019362
AN - SCOPUS:84866847266
SN - 0027-8424
VL - 109
SP - 15787
EP - 15792
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 39
ER -