title: The Rho-specific GAP protein DLC3 coordinates endocytic membrane trafficking.
abstract: Membrane trafficking is known to be coordinated by small GTPases, but the identity of their regulators, the guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that ensure balanced GTPase activation at different subcellular sites is largely elusive. Here, we show in living cells that deleted in liver cancer 3 (DLC3, also known as STARD8) is a functional Rho-specific GAP protein, the loss of which enhances perinuclear RhoA activity. DLC3 is recruited to Rab8-positive membrane tubules and is required for the integrity of the Rab8 and Golgi compartments. Depletion of DLC3 impairs the transport of internalized transferrin to the endocytic recycling compartment (ERC), which is restored by the simultaneous downregulation of RhoA and RhoB. We further demonstrate that DLC3 loss interferes with epidermal growth factor receptor (EGFR) degradation associated with prolonged receptor signaling. Taken together, these findings identify DLC3 as a novel component of the endocytic trafficking machinery, wherein it maintains organelle integrity and regulates membrane transport through the control of Rho activity.
authors: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors: Anja C
authors: AC
authors: Braun
authors: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors: Janina
authors: J
authors: Hendrick
authors: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors: Stephan A
authors: SA
authors: Eisler
authors: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors: Simone
authors: S
authors: Schmid
authors: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors: Angelika
authors: A
authors: Hausser
authors: Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany monilola.olayioye@izi.uni-stuttgart.de.
authors: Monilola A
authors: MA
authors: Olayioye
mesh_terms: D004705:Endocytosis; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D014168:Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; C000606740:STARD8 protein, human; D014168:Transferrin; D066246:ErbB Receptors; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein
keywords: EGFR signaling; Endocytosis; Rab8; Rho GTPase-activating protein; Tumor suppressor