TY - JOUR T1 - Axonally Synthesized β-Actin and GAP-43 Proteins Support Distinct Modes of Axonal Growth JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3311 LP - 3322 DO - 10.1523/JNEUROSCI.1722-12.2013 VL - 33 IS - 8 AU - Christopher J. Donnelly AU - Michael Park AU - Mirela Spillane AU - Soonmoon Yoo AU - Almudena Pacheco AU - Cynthia Gomes AU - Deepika Vuppalanchi AU - Marguerite McDonald AU - Hak Hee Kim AU - Tanuja T. Merianda AU - Gianluca Gallo AU - Jeffery L. Twiss Y1 - 2013/02/20 UR - http://www.jneurosci.org/content/33/8/3311.abstract N2 - Increasing evidence points to the importance of local protein synthesis for axonal growth and responses to axotomy, yet there is little insight into the functions of individual locally synthesized proteins. We recently showed that expression of a reporter mRNA with the axonally localizing β-actin mRNA 3′UTR competes with endogenous β-actin and GAP-43 mRNAs for binding to ZBP1 and axonal localization in adult sensory neurons (Donnelly et al., 2011). Here, we show that the 3′UTR of GAP-43 mRNA can deplete axons of endogenous β-actin mRNA. We took advantage of this 3′UTR competition to address the functions of axonally synthesized β-actin and GAP-43 proteins. In cultured rat neurons, increasing axonal synthesis of β-actin protein while decreasing axonal synthesis of GAP-43 protein resulted in short highly branched axons. Decreasing axonal synthesis of β-actin protein while increasing axonal synthesis of GAP-43 protein resulted in long axons with few branches. siRNA-mediated depletion of overall GAP-43 mRNA from dorsal root ganglia (DRGs) decreased the length of axons, while overall depletion of β-actin mRNA from DRGs decreased the number of axon branches. These deficits in axon growth could be rescued by transfecting with siRNA-resistant constructs encoding β-actin or GAP-43 proteins, but only if the mRNAs were targeted for axonal transport. Finally, in ovo electroporation of axonally targeted GAP-43 mRNA increased length and axonally targeted β-actin mRNA increased branching of sensory axons growing into the chick spinal cord. These studies indicate that axonal translation of β-actin mRNA supports axon branching and axonal translation of GAP-43 mRNA supports elongating growth. ER -