The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions.
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.
Yamamura
Rie
R
Department of Biochemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Nishimura
Noriyuki
N
Nakatsuji
Hiroyoshi
H
Arase
Seiji
S
Sasaki
Takuya
T
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*
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