MAP1A light chain-2 interacts with GTP-RhoB to control epidermal growth factor (EGF)-dependent EGF receptor signaling.
Rho GTPases have been implicated in the control of several cellular functions, including regulation of the actin cytoskeleton, cell proliferation, and oncogenesis. Unlike RhoA and RhoC, RhoB localizes in part to endosomes and controls endocytic trafficking. Using a yeast two-hybrid screen and a glutathione S-transferase pulldown assay, we identified LC2, the light chain of the microtubule-associated protein MAP1A, as a novel binding partner for RhoB. GTP binding and the 18-amino acid C-terminal hypervariable domain of RhoB are critical for its binding to MAP1A/LC2. Coimmunoprecipitation and immunofluorescence experiments showed that this interaction occurs in U87 cells. Down-regulation of MAP1A/LC2 expression decreased epidermal growth factor (EGF) receptor expression and modified the signaling response to EGF treatment. We concluded that MAP1A/LC2 is critical for RhoB function in EGF-induced EGF receptor regulation. Because MAP1A/LC2 is thought to function as an adaptor between microtubules and other molecules, we postulate that the RhoB and MAP1A/LC2 interactions facilitate endocytic vesicle trafficking and regulate the trafficking of signaling molecules.
Lajoie-Mazenc
Isabelle
I
INSERM U563, Département Oncogénèse, Signalisation et Innovation Thérapeutique, Toulouse F-31059, France. lajoie.isabelle@claudiusregaud.fr
Tovar
Daniel
D
Penary
Marie
M
Lortal
Barbara
B
Allart
Sophie
S
Favard
Cyril
C
Brihoum
Meryem
M
Pradines
Anne
A
Favre
Gilles
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D034741:RNA, Small Interfering; D015398:Signal Transduction; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D006160:Guanosine Triphosphate; D066246:ErbB Receptors; D020743:rhoB GTP-Binding Protein