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: Anja C Braun, Janina Hendrick, Stephan A Eisler, Simone Schmid, Angelika Hausser, Monilola A Olayioye
• Journal: Journal of cell science (J Cell Sci) Vol. 128 Issue 7 Pg. 1386-99 (Apr 01 2015) ISSN: 1477-9137 [Electronic] England
• PMID: 25673874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015. Published by The Company of Biologists Ltd.

Chemical References

• GTPase-Activating Proteins
• STARD8 protein, human
• Transferrin
• ErbB Receptors
• RAB8A protein, human
• rab GTP-Binding Proteins
• rhoA GTP-Binding Protein
• rhoB GTP-Binding Protein

Topics

• Endocytosis
• ErbB Receptors (genetics, metabolism)
• GTPase-Activating Proteins (genetics, metabolism)
• Golgi Apparatus (genetics, metabolism)
• HeLa Cells
• Humans
• Protein Binding
• Protein Transport
• Transferrin (metabolism)
• rab GTP-Binding Proteins (genetics, metabolism)
• rhoA GTP-Binding Protein (genetics, metabolism)
• rhoB GTP-Binding Protein (genetics, metabolism)