Crescerin uses a TOG domain array to regulate microtubules in the primary cilium |
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| Authors: | Alakananda Das Daniel J Dickinson Cameron C Wood Bob Goldstein Kevin C Slep |
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| Institution: | Harvard Medical School;aDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599;bMolecular and Cellular Biophysics Program, University of North Carolina, Chapel Hill, NC 27599;cDepartment of Biology, University of North Carolina, Chapel Hill, NC 27599;dLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 |
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| Abstract: | Eukaryotic cilia are cell-surface projections critical for sensing the extracellular environment. Defects in cilia structure and function result in a broad range of developmental and sensory disorders. However, mechanisms that regulate the microtubule (MT)-based scaffold forming the cilia core are poorly understood. TOG domain array–containing proteins ch-TOG and CLASP are key regulators of cytoplasmic MTs. Whether TOG array proteins also regulate ciliary MTs is unknown. Here we identify the conserved Crescerin protein family as a cilia-specific, TOG array-containing MT regulator. We present the crystal structure of mammalian Crescerin1 TOG2, revealing a canonical TOG fold with conserved tubulin-binding determinants. Crescerin1''s TOG domains possess inherent MT-binding activity and promote MT polymerization in vitro. Using Cas9-triggered homologous recombination in Caenorhabditis elegans, we demonstrate that the worm Crescerin family member CHE-12 requires TOG domain–dependent tubulin-binding activity for sensory cilia development. Thus, Crescerin expands the TOG domain array–based MT regulatory paradigm beyond ch-TOG and CLASP, representing a distinct regulator of cilia structure. |
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