title: Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.
abstract: Microtubule actin crosslinking factor 1 (MACF1) plays a role in the coordination of microtubules and actin in multiple cellular processes. Here, we show that MACF1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis, and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized, while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of MACF1 in adult photoreceptors causes reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for MACF1 function. MACF1 also interacts with the ciliary proteins MKKS and TALPID3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking MACF1 and that MKKS and TALPID3 are involved in the coordination of microtubule and actin interactions.
authors: National Eye Institute, Bethesda, MD 20892, USA. Electronic address: hmaysime@uni-mainz.de.
authors: Helen L
authors: HL
authors: May-Simera
authors: National Eye Institute, Bethesda, MD 20892, USA.
authors: Jessica D
authors: JD
authors: Gumerson
authors: National Eye Institute, Bethesda, MD 20892, USA.
authors: Chun
authors: C
authors: Gao
authors: National Eye Institute, Bethesda, MD 20892, USA.
authors: Maria
authors: M
authors: Campos
authors: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
authors: Stephanie M
authors: SM
authors: Cologna
authors: Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Tina
authors: T
authors: Beyer
authors: Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany.
authors: Karsten
authors: K
authors: Boldt
authors: National Eye Institute, Bethesda, MD 20892, USA.
authors: Koray D
authors: KD
authors: Kaya
authors: National Eye Institute, Bethesda, MD 20892, USA.
authors: Nisha
authors: N
authors: Patel
authors: National Eye Institute, Bethesda, MD 20892, USA.
authors: Friedrich
authors: F
authors: Kretschmer
authors: National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA.
authors: Matthew W
authors: MW
authors: Kelley
authors: National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA.
authors: Ronald S
authors: RS
authors: Petralia
authors: The Roslin Institute, University of Edinburgh, Roslin, Midlothian EH25 9RG, UK.
authors: Megan G
authors: MG
authors: Davey
authors: National Eye Institute, Bethesda, MD 20892, USA. Electronic address: tiansen.li@nih.gov.
authors: Tiansen
authors: T
authors: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D064652:Basal Bodies / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation; D016764:Cell Polarity; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D006706:Homeostasis; D008840:Microfilament Proteins / Q000172:deficiency* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D038081:Organogenesis; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*
chemical_list: C490632:Macf1 protein, mouse; D008840:Microfilament Proteins
keywords: actin; basal body; centrosome; cilia; ciliogenesis; ciliopathy; microtubule; polarity; retina; retinal degeneration