| First Author | Das A | Year | 2015 |
| Journal | Mol Biol Cell | Volume | 26 |
| Issue | 23 | Pages | 4248-64 |
| PubMed ID | 26378256 | Mgi Jnum | J:235315 |
| Mgi Id | MGI:5796072 | Doi | 10.1091/mbc.E15-08-0603 |
| Citation | Das A, et al. (2015) Crescerin uses a TOG domain array to regulate microtubules in the primary cilium. Mol Biol Cell 26(23):4248-64 |
| abstractText | 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. |
