GLUT1CBP(TIP2/GIPC1) interactions with GLUT1 and myosin VI: evidence supporting an adapter function for GLUT1CBP.
We identified a novel interaction between myosin VI and the GLUT1 transporter binding protein GLUT1CBP(GIPC1) and first proposed that as an adapter molecule it might function to couple vesicle-bound proteins to myosin VI movement. This study refines the model by identifying two myosin VI binding domains in the GIPC1 C terminus, assigning respective oligomerization and myosin VI binding functions to separate N- and C-terminal domains, and defining a central region in the myosin VI tail that binds GIPC1. Data further supporting the model demonstrate that 1) myosin VI and GIPC1 interactions do not require a mediating protein; 2) the myosin VI binding domain in GIPC1 is necessary for intracellular interactions of GIPC1 with myosin VI and recruitment of overexpressed myosin VI to membrane structures, but not for the association of GIPC1 with such structures; 3) GIPC1/myosin VI complexes coordinately move within cellular extensions of the cell in an actin-dependent and microtubule-independent manner; and 4) blocking either GIPC1 interactions with myosin VI or GLUT1 interactions with GIPC1 disrupts normal GLUT1 trafficking in polarized epithelial cells, leading to a reduction in the level of GLUT1 in the plasma membrane and concomitant accumulation in internal membrane structures.
Reed
Brent C
BC
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. breed@lsuhsc.edu
Cefalu
Christopher
C
Bellaire
Bryan H
BH
Cardelli
James A
JA
Louis
Thomas
T
Salamon
Joanna
J
Bloecher
Mari Anne
MA
Bunn
Robert C
RC
D000199:Actins / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492009:GIPC1 protein, human; D009479:Neuropeptides; C089785:myosin VI; D018995:Myosin Heavy Chains