title: MICAL-like1 in endosomal signaling.
abstract: Small GTPase Rabs are required for membrane protein sorting/delivery to precise membrane domains. Rab13 regulates tight junction assembly and polarized membrane transport in epithelial cells. Using yeast two-hybrid screen, we identified MICAL-like1 (MICAL-L1), a protein that interacts with GTP-bound Rab13 and shares a similar domain organization with MICAL protein family. MICAL-L1 has a calponin homology, Lin11, Isl-1 & Mec-3 (LIM), proline-rich, and coiled-coil domains. It is associated with late and recycling endosomes. Time-lapse video microscopy shows that GFP-Rab7 and cherry-MICAL-L1 are present within vesicles that move rapidly in the cytoplasm. Depletion of MICAL-L1 by short hairpin RNA does not alter the distribution of tight junction proteins, but affects the trafficking of epidermal growth factor receptor (EGFR). Overexpression of MICAL-L1 leads to the accumulation of EGFR in late endosomal compartments. In contrast, knocking down MICAL-L1 results in the distribution of internalized EGFR in vesicles spread throughout the cytoplasm and promotes its degradation. Our data show that MICAL-L1 inhibits EGFR degradation, suggesting that MICAL-L1 is involved in sorting/targeting the receptor to the recycling pathway. They provide novel insights into MICAL-L1/Rab protein complex that can regulate EGFR trafficking/signaling.
authors.affiliation: Phagocytosis and Bacterial Invasion Laboratory, INSERM U.1016-CNRS UMR8104, Institut Cochin, Université Paris Descartes, Paris, France. Electronic address: ahmed.zahraoui@inserm.fr.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Zahraoui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004285:Dogs; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D060588:LIM Domain Proteins / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D008840:Microfilament Proteins; D008856:Microscopy, Fluorescence; D006899:Mixed Function Oxygenases; D021381:Protein Transport; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D000096985:Calponins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000242:Cyclic AMP; D003598:Cytoskeletal Proteins; D066246:ErbB Receptors; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D034741:RNA, Small Interfering; C455272:MICAL1 protein, human; D000096985:Calponins; C512478:EGFR protein, human
keywords: EGFR; Effector; Endocytosis; Membrane traffic; Protein–protein interaction; Small Rab GTPases