Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina

Cell Rep. 2016 Oct 25;17(5):1399-1413. doi: 10.1016/j.celrep.2016.09.089.

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.

Keywords: actin; basal body; centrosome; cilia; ciliogenesis; ciliopathy; microtubule; polarity; retina; retinal degeneration.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Basal Bodies / metabolism
  • Basal Bodies / ultrastructure
  • Cell Differentiation
  • Cell Polarity*
  • Centrioles / metabolism
  • Centrioles / ultrastructure
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Homeostasis
  • Microfilament Proteins / deficiency*
  • Microfilament Proteins / metabolism
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mutation / genetics
  • Organogenesis*
  • Photoreceptor Cells, Vertebrate / cytology
  • Photoreceptor Cells, Vertebrate / metabolism
  • Retina / cytology*
  • Retina / growth & development
  • Retina / metabolism*

Substances

  • Macf1 protein, mouse
  • Microfilament Proteins