title: MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a.
abstract: Endocytosis is a conserved process across species in which cell surface receptors and lipids are internalized from the plasma membrane. Once internalized, receptors can either be degraded or be recycled back to the plasma membrane. A variety of small GTP-binding proteins regulate receptor recycling. Despite our familiarity with many of the key regulatory proteins involved in this process, our understanding of the mode by which these proteins co-operate and the sequential manner in which they function remains limited. In this study, we identify two GTP-binding proteins as interaction partners of the endocytic regulatory protein molecule interacting with casl-like protein 1 (MICAL)-L1. First, we demonstrate that Rab35 is a MICAL-L1-binding partner in vivo. Over-expression of active Rab35 impairs the recruitment of MICAL-L1 to tubular recycling endosomes, whereas Rab35 depletion promotes enhanced MICAL-L1 localization to these structures. Moreover, we demonstrate that Arf6 forms a complex with MICAL-L1 and plays a role in its recruitment to tubular endosomes. Overall, our data suggest a model in which Rab35 is a critical upstream regulator of MICAL-L1 and Arf6, while both MICAL-L1 and Arf6 regulate Rab8a function.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
authors.forename: Juliati
authors.initials: J
authors.lastname: Rahajeng
authors.forename: Sai Srinivas Panapakkam
authors.initials: SS
authors.lastname: Giridharan
authors.forename: Bishuang
authors.initials: B
authors.lastname: Cai
authors.forename: Naava
authors.initials: N
authors.lastname: Naslavsky
authors.forename: Steve
authors.initials: S
authors.lastname: Caplan
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D018613:Microscopy, Confocal; D006899:Mixed Function Oxygenases; D021381:Protein Transport; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000096985:Calponins
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D020691:rab GTP-Binding Proteins; C455272:MICAL1 protein, human; D000096985:Calponins; C511183:RAB35 protein, human; C082377:RAB8A protein, human; C000715348:ARF6 protein, human