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Crescerin uses a TOG domain array to regulate microtubules in the primary cilium

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 p...

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Autores principales: Das, Alakananda, Dickinson, Daniel J., Wood, Cameron C., Goldstein, Bob, Slep, Kevin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642858/
https://www.ncbi.nlm.nih.gov/pubmed/26378256
http://dx.doi.org/10.1091/mbc.E15-08-0603
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author Das, Alakananda
Dickinson, Daniel J.
Wood, Cameron C.
Goldstein, Bob
Slep, Kevin C.
author_facet Das, Alakananda
Dickinson, Daniel J.
Wood, Cameron C.
Goldstein, Bob
Slep, Kevin C.
author_sort Das, Alakananda
collection PubMed
description 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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spelling pubmed-46428582016-01-30 Crescerin uses a TOG domain array to regulate microtubules in the primary cilium Das, Alakananda Dickinson, Daniel J. Wood, Cameron C. Goldstein, Bob Slep, Kevin C. Mol Biol Cell Articles 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. The American Society for Cell Biology 2015-11-15 /pmc/articles/PMC4642858/ /pubmed/26378256 http://dx.doi.org/10.1091/mbc.E15-08-0603 Text en © 2015 Das et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Das, Alakananda
Dickinson, Daniel J.
Wood, Cameron C.
Goldstein, Bob
Slep, Kevin C.
Crescerin uses a TOG domain array to regulate microtubules in the primary cilium
title Crescerin uses a TOG domain array to regulate microtubules in the primary cilium
title_full Crescerin uses a TOG domain array to regulate microtubules in the primary cilium
title_fullStr Crescerin uses a TOG domain array to regulate microtubules in the primary cilium
title_full_unstemmed Crescerin uses a TOG domain array to regulate microtubules in the primary cilium
title_short Crescerin uses a TOG domain array to regulate microtubules in the primary cilium
title_sort crescerin uses a tog domain array to regulate microtubules in the primary cilium
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642858/
https://www.ncbi.nlm.nih.gov/pubmed/26378256
http://dx.doi.org/10.1091/mbc.E15-08-0603
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