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Helen May-Simera, Jessica Gumerson, Chun Gao, Maria M Campos, Tiansen Li; Loss of Macf1 abolishes ciliogenesis and disrupts apicobasal polarity establishment in the retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):116.
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© ARVO (1962-2015); The Authors (2016-present)
Microtubule actin crosslinking factor 1 (Macf1) plays a role in coordinated actions of actin and microtubules in multiple cellular processes. It is widely known for its coordination of microtubules and actin at focal adhesions. A previous study identified Macf1 as an interacting partner with ciliary protein Mkks (Bbs6). We therefore sought to examine whether Macf1 is required for cilia function, particularly in the ciliated photoreceptor cells of the retina.
We ablated Macf1 in select tissues and show that Macf1 is essential for cilia biogenesis and maintenance. We used multiple conditional knockout strains to examine functional and developmental defects in brain, cochlear, and retinal tissues upon loss of Macf1. A Macf1 null cell line was also generated to study Macf1 involvement in ciliogenesis and potential interactions with other ciliary proteins.
We show that Macf1 is 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 found that MACF1 is required for apical basal body docking and ciliogenesis, and is thereby critical for maintenance of the photoreceptor sensory cilium. Thus primary cilia may provide positional cues for apicobasal polarization of photoreceptors. We also 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.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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