PMID- 16980965 OWN - NLM STAT- MEDLINE DCOM- 20061114 LR - 20161019 IS - 1097-6256 (Print) IS - 1097-6256 (Linking) VI - 9 IP - 10 DP - 2006 Oct TI - An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance. PG - 1265-73 AB - Axon pathfinding requires directional responses of growth cones to extracellular cues, which have been shown to involve local synthesis of protein. The identity and functions of the locally produced proteins remain, however, unclear. Here we report that Ca(2+)-dependent bidirectional turning of Xenopus laevis growth cones requires localized distribution and translation of beta-actin messenger RNA. Both beta-actin mRNA and its zipcode-binding protein, ZBP1, are localized at the growth cone and become asymmetrically distributed upon local exposure to brain-derived neurotrophic factor (BDNF). Inhibition of protein synthesis or antisense interference with beta-actin mRNA-ZBP1 binding abolishes both Ca(2+)-mediated attraction and repulsion. In addition, attraction involves a local increase in beta-actin, whereas repulsion is accompanied by a local decrease in beta-actin; thus, both produce a synthesis- and ZBP1 binding-dependent beta-actin asymmetry but with opposite polarities. Together with a similar asymmetry in Src activity during bidirectional responses, our findings indicate that Ca(2+)-dependent spatial regulation of beta-actin synthesis through Src contributes to the directional motility of growth cones during guidance. FAU - Yao, Jiaqi AU - Yao J AD - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA. FAU - Sasaki, Yukio AU - Sasaki Y FAU - Wen, Zhexing AU - Wen Z FAU - Bassell, Gary J AU - Bassell GJ FAU - Zheng, James Q AU - Zheng JQ LA - eng GR - R29 NS036241/NS/NINDS NIH HHS/United States GR - HD46368/HD/NICHD NIH HHS/United States GR - NS36241/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060917 PL - United States TA - Nat Neurosci JT - Nature neuroscience JID - 9809671 RN - 0 (Actins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Glycoproteins) RN - 0 (RNA, Messenger) RN - SY7Q814VUP (Calcium) SB - IM CIN - Nat Neurosci. 2006 Oct;9(10):1201-3. PMID: 17001333 MH - Actins/*genetics MH - Animals MH - Blotting, Western/methods MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Calcium/*metabolism MH - Cells, Cultured MH - Drug Interactions MH - Embryo, Nonmammalian MH - Enzyme Inhibitors/pharmacology MH - Fluorescent Antibody Technique/methods MH - Glycoproteins/genetics/metabolism MH - Growth Cones/drug effects/*physiology MH - In Situ Hybridization/methods MH - Neurons/*cytology/physiology MH - Protein Biosynthesis/drug effects/*physiology MH - RNA, Messenger/*physiology MH - Time Factors MH - Xenopus laevis EDAT- 2006/09/19 09:00 MHDA- 2006/11/15 09:00 CRDT- 2006/09/19 09:00 PHST- 2006/07/18 00:00 [received] PHST- 2006/08/23 00:00 [accepted] PHST- 2006/09/19 09:00 [pubmed] PHST- 2006/11/15 09:00 [medline] PHST- 2006/09/19 09:00 [entrez] AID - nn1773 [pii] AID - 10.1038/nn1773 [doi] PST - ppublish SO - Nat Neurosci. 2006 Oct;9(10):1265-73. doi: 10.1038/nn1773. Epub 2006 Sep 17.