title: Doublecortin recognizes the longitudinal curvature of the microtubule end and lattice.
abstract: BACKGROUND
  Microtubule ends have distinct biochemical and structural features from those of the lattice. Several proteins that control microtubule behavior can distinguish the end of a microtubule from the lattice. The end-binding protein EB1, for example, recognizes the nucleotide state of microtubule ends, which are enriched in GTP-tubulin. EB1 shares its binding site with Doublecortin (DCX), a protein expressed in developing neurons. We showed recently that DCX binds with highest affinity to microtubule ends.
  
  
  RESULTS
  Here we show that DCX recognizes microtubule ends by a novel mechanism based on lattice curvature. Using single-molecule microscopy, we show that DCX "comets" do not elongate at faster microtubule growth rates and DCX does not recognize two out of three GTP analogs. We demonstrate that DCX binds with higher affinity to curved microtubule lattices than to straight ones. We find that curvature recognition is a property of single DCX molecules. Straightening of protofilaments (pfs) at microtubule ends with paclitaxel significantly attenuates end-recognition by DCX, but not EB1. Mutations in DCX found in patients with double cortex syndrome disrupted curvature recognition.
  
  
  CONCLUSIONS
  We propose a model in which DCX recognizes microtubule ends through specific interactions with their structure. We conclude that microtubule ends have two distinct features that proteins can recognize independently, namely a structural feature related to curvature and nucleotide state.
authors.affiliation: Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bechstedt
authors.affiliation: Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada.
authors.forename: Kevan
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada. Electronic address: gary.brouhard@mcgill.ca.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Brouhard
mesh_terms: D000818:Animals; D002417:Cattle; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000502:physiology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D006160:Guanosine Triphosphate