title: Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions.
abstract: The adherens junction (AJ) plays a crucial role in maintaining cell-cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end-directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule minus ends. The function of junction-associated KIFC3, however, remains to be elucidated. Here we find that KIFC3 binds the ubiquitin-specific protease USP47, a protease that removes ubiquitin chains from substrates and hence inhibits proteasome-mediated proteolysis, and recruits it to AJs. Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region of the cytoplasmic domain, resulting in the production of a 90-kDa fragment and the internalization of E-cadherin. This cleavage depends on the E3 ubiquitin protein ligase Hakai and is inhibited by proteasome inhibitors. E-cadherin ubiquitination consistently increases after depletion of KIFC3 or USP47. These findings suggest that KIFC3 suppresses the ubiquitination and resultant degradation of E-cadherin by recruiting USP47 to AJs, a process that may be involved in maintaining stable cell-cell adhesion in epithelial sheets.
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sako-Kubota
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagae
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Meng
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan takeichi@cdb.riken.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeichi
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D015153:Blotting, Western; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D034622:RNA Interference; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
chemical_list: D015820:Cadherins; C586505:Kifc3 protein, human; C557800:USP47 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D046988:Proteasome Endopeptidase Complex; D016547:Kinesins