title: Direct binding of TUBB3 with DCC couples netrin-1 signaling to intracellular microtubule dynamics in axon outgrowth and guidance.
abstract: The coupling of axon guidance cues, such as netrin-1, to microtubule (MT) dynamics is essential for growth cone navigation in the developing nervous system. However, whether axon guidance signaling regulates MT dynamics directly or indirectly is unclear. Here, we report that TUBB3, the most dynamic β-tubulin isoform in neurons, directly interacts with the netrin receptor DCC, and that netrin-1 induces this interaction in primary neurons. TUBB3 colocalizes with DCC in the growth cones of primary neurons and MT dynamics is required for netrin-1-promoted association of TUBB3 with DCC. Netrin-1 not only increases co-sedimentation of DCC with polymerized MT, but also promotes MT dynamics in the growth cone. Knocking down TUBB3 inhibits netrin-1-induced MT dynamics, axon outgrowth and attraction in vitro and causes defects in commissural axon projection in the embryo. These results indicate that TUBB3 directly links netrin signaling pathways to MT dynamics and plays an important role in guiding commissural axons in vivo.
authors: Department of Biological Sciences, University of Toledo, M.S. 601, 2801 W. Bancroft Street, Toledo, OH 43606, USA.
authors: Chao
authors: C
authors: Qu
authors: Trisha
authors: T
authors: Dwyer
authors: Qiangqiang
authors: Q
authors: Shao
authors: Tao
authors: T
authors: Yang
authors: Huai
authors: H
authors: Huang
authors: Guofa
authors: G
authors: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D048708:Cell Growth Processes / Q000235:genetics; D002642:Chick Embryo; D000075389:DCC Receptor; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D000075388:Netrin-1; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C462941:beta3 tubulin, mouse; D000075388:Netrin-1
keywords: Axon guidance; DCC; Microtubule dynamics; Netrin; Signal transduction; TUBB3
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