5dn7

Publication Abstract from PubMed

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 have identified 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.

Crescerin uses a TOG domain array to regulate microtubules in the primary cilium.,Das A, Dickinson DJ, Wood CC, Goldstein B, Slep KC Mol Biol Cell. 2015 Sep 16. pii: mbc.E15-08-0603. PMID:26378256^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.