KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC.
Epithelial polarization is associated with selective stabilization and reorganization of microtubule (MT) arrays. However, upstream events and downstream consequences of MT stabilization during epithelial morphogenesis are still unclear. We show that the anterograde kinesin KIF17 localizes to MT plus ends, stabilizes MTs, and affects epithelial architecture. Targeting of KIF17 to plus ends of growing MTs requires kinesin motor activity and interaction with EB1. In turn, KIF17 participates in localizing adenomatous polyposis coli (APC) to the plus ends of a subset of MTs. We found that KIF17 affects MT dynamics, polymerization rates, and MT plus end stabilization to generate posttranslationally acetylated MTs. Depletion of KIF17 from cells growing in three-dimensional matrices results in aberrant epithelial cysts that fail to generate a single central lumen and to polarize apical markers. These findings implicate KIF17 in MT stabilization events that contribute to epithelial polarization and morphogenesis.
Jaulin
Fanny
F
Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA.
Kreitzer
Geri
G
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009024:Morphogenesis
D025601:Adenomatous Polyposis Coli Protein; C485813:KIF17 protein, human; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D016547:Kinesins