title: DSCR1 is required for both axonal growth cone extension and steering.
abstract: Local information processing in the growth cone is essential for correct wiring of the nervous system. As an axon navigates through the developing nervous system, the growth cone responds to extrinsic guidance cues by coordinating axon outgrowth with growth cone steering. It has become increasingly clear that axon extension requires proper actin polymerization dynamics, whereas growth cone steering involves local protein synthesis. However, molecular components integrating these two processes have not been identified. Here, we show that Down syndrome critical region 1 protein (DSCR1) controls axon outgrowth by modulating growth cone actin dynamics through regulation of cofilin activity (phospho/dephospho-cofilin). Additionally, DSCR1 mediates brain-derived neurotrophic factor-induced local protein synthesis and growth cone turning. Our study identifies DSCR1 as a key protein that couples axon growth and pathfinding by dually regulating actin dynamics and local protein synthesis.
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.
authors.forename: Asit
authors.initials: A
authors.lastname: Rai
authors.affiliation: Brain Science Institute-Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Korea Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, Korea Department of Neuroscience, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Hur
authors.affiliation: Anima Biotech, Ltd., Tel-Aviv 69710, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Smilansky
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90089 Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90089.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Chang
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea ktaimin@unist.ac.kr.
authors.forename: Kyung-Tai
authors.initials: KT
authors.lastname: Min
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D020439:Growth Cones / Q000378:metabolism* / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology
chemical_list: D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins