title: The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions.
abstract: The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJs. Here, we investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca(2+)-switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.
authors: Department of Biochemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors: Rie
authors: R
authors: Yamamura
authors: Noriyuki
authors: N
authors: Nishimura
authors: Hiroyoshi
authors: H
authors: Nakatsuji
authors: Seiji
authors: S
authors: Arase
authors: Takuya
authors: T
authors: Sasaki
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D062445:Claudin-1; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins; D008954:Models, Biological; D062793:Occludin; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D019108:Tight Junctions / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; C568113:Cldn1 protein, mouse; D003598:Cytoskeletal Proteins; C512298:JRAB protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; C521976:Rab8 protein, mouse; D020691:rab GTP-Binding Proteins