RhoD regulates endosome dynamics through Diaphanous-related Formin and Src tyrosine kinase.
Early endosomes move bidirectionally between the cell periphery and the interior through a mechanism regulated by the low molecular weight GTPase RhoD. Here, we identify a novel splice variant of human Diaphanous, hDia2C, which specifically binds to RhoD and is recruited onto early endosomes. Expression of RhoD and hDia2C induces a striking alignment of early endosomes along actin filaments and reduces their motility. This activity depends on the membrane recruitment and activation of c-Src kinase, thus uncovering a new role in endosome function. Our results define a novel signal transduction pathway, in which hDia2C and c-Src are sequentially activated by RhoD to regulate the motility of early endosomes through interactions with the actin cytoskeleton.
Gasman
Stéphane
S
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden D-01307, Germany.
Kalaidzidis
Yannis
Y
Zerial
Marino
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004705:Endocytosis; D011992:Endosomes / Q000502:physiology*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D020741:rho GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; C491462:DIAPH2 protein, human; D017931:DNA Primers; D000080865:Formins; D019061:src-Family Kinases; C105243:RHOD protein, human; D020741:rho GTP-Binding Proteins