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Doublecortin is excluded from growing microtubule ends and recognizes the GDP-microtubule lattice.
Curr. Biol. 26, 1549-1555 (2016)
Many microtubule (MT) functions are mediated by a diverse class of proteins (+TIPs) at growing MT plus ends that control intracellular MT interactions and dynamics and depend on end-binding proteins (EBs) . Cryoelectron microscopy has recently identified the EB binding site as the interface of four tubulin dimers that undergoes a conformational change in response to β-tubulin GTP hydrolysis [2, 3]. Doublecortin (DCX), a MT-associated protein (MAP) required for neuronal migration during cortical development [4, 5], binds to the same site as EBs , and recent in vitro studies proposed DCX localization to growing MT ends independent of EBs . Because this conflicts with observations in neurons [8, 9] and the molecular function of DCX is not well understood, we revisited intracellular DCX dynamics at low expression levels. Here, we report that DCX is not a +TIP in cells but, on the contrary, is excluded from the EB1 domain. In addition, we find that DCX-MT interactions are highly sensitive to MT geometry. In cells, DCX binding was greatly reduced at MT segments with high local curvature. Remarkably, this geometry-dependent binding to MTs was completely reversed in the presence of taxanes, which reconciles incompatible observations in cells  and in vitro . We propose a model explaining DCX specificity for different MT geometries based on structural changes induced by GTP hydrolysis that decreases the spacing between adjacent tubulin dimers . Our data are consistent with a unique mode of MT interaction in which DCX specifically recognizes this compacted GDP-like MT lattice. Ettinger et al. report that the neuronal migration protein doublecortin (DCX) is an "anti-+TIP" in cells that is excluded from growing microtubule (MT) ends. DCX preferentially binds to straight MTs in the absence but to curved MT segments in the presence of taxanes, supporting a model in which DCX recognizes the compacted GDP-like MT lattice.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gtp Hydrolysis; Dynamics; Transitions; Resolution; Proteins; Kinase; Eb1
ISSN (print) / ISBN 0960-9822
Journal Current Biology
Quellenangaben Volume: 26, Issue: 12, Pages: 1549-1555
Publishing Place Cambridge
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)