title: A Mec17-Myosin II Effector Axis Coordinates Microtubule Acetylation and Actin Dynamics to Control Primary Cilium Biogenesis.
abstract: Primary cilia are specialized, acetylated microtubule-based signaling processes. Cilium assembly is activated by cellular quiescence and requires reconfiguration of microtubules, the actin cytoskeleton, and vesicular trafficking machinery. How these components are coordinated to activate ciliogenesis remains unknown. Here we identify the microtubule acetyltransferase Mec-17 and myosin II motors as the key effectors in primary cilium biogenesis. We found that myosin IIB (Myh10) is required for cilium formation; however, myosin IIA (Myh9) suppresses it. Myh10 binds and antagonizes Myh9 to increase actin dynamics, which facilitates the assembly of the pericentrosomal preciliary complex (PPC) that supplies materials for cilium growth. Importantly, Myh10 expression is upregulated by serum-starvation and this induction requires Mec-17, which is itself accumulated upon cellular quiescence. Pharmacological stimulation of microtubule acetylation also induces Myh10 expression and cilium formation. Thus cellular quiescence induces Mec17 to couple the production of acetylated microtubules and Myh10, whose accumulation overcomes the inhibitory role of Myh9 and initiates ciliogenesis.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Rao
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Hao
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Tso-Pang
authors.initials: TP
authors.lastname: Yao
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D008868:Microtubule Proteins; D008870:Microtubules / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D024462:Myosin Type II / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics
chemical_list: D000199:Actins; D008868:Microtubule Proteins; D000123:Acetyltransferases; C000627069:ATAT1 protein, human; D024462:Myosin Type II; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains