title: Crescerin uses a TOG domain array to regulate microtubules in the primary cilium.
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.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 Molecular and Cellular Biophysics Program, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Alakananda
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dickinson
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Wood
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Bob
authors.initials: B
authors.lastname: Goldstein
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599 kslep@bio.unc.edu.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Slep
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D002923:Cilia / Q000378:metabolism*; D017124:Conserved Sequence; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D014404:Tubulin