Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Phosphorylation of zipcode binding protein 1 is required for brain-derived neurotrophic factor signaling of local beta-actin synthesis and growth cone turning.
Sasaki Y
,
Welshhans K
,
Wen Z
,
Yao J
,
Xu M
,
Goshima Y
,
Zheng JQ
,
Bassell GJ
.
???displayArticle.abstract???
The localization of specific mRNAs and their local translation in growth cones of developing axons has been shown to play an important mechanism to regulate growth cone turning responses to attractive or repulsive cues. However, the mechanism whereby local translation and growth cone turning may be controlled by specific mRNA-binding proteins is unknown. Here we demonstrate that brain-derived neurotrophic factor (BDNF) signals the Src-dependent phosphorylation of the beta-actin mRNA zipcode binding protein 1 (ZBP1), which is necessary for beta-actin synthesis and growth cone turning. We raised a phospho-specific ZBP1 antibody to Tyr396, which is a Src phosphorylation site, and immunofluorescence revealed BDNF-induced phosphorylation of ZBP1 within growth cones. The BDNF-induced increase in fluorescent signal of a green fluorescent protein translation reporter with the 3' untranslated region of beta-actin was attenuated with the Src family kinase-specific inhibitor PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine]. Furthermore, a nonphosphorylatable mutant, ZBP1 Y396F, suppressed the BDNF-induced and protein synthesis-dependent increase in beta-actin localization in growth cones. Last, the ZBP1 Y396F mutant blocked BDNF-induced attractive growth cone turning. These results indicate that phosphorylation of ZBP1 at Tyr396 within growth cones has a critical role to regulate local protein synthesis and growth cone turning. Our findings provide new insight into how the regulated phosphorylation of mRNA-binding proteins influences local translation underlying growth cone motility and axon guidance.
Aakalu,
Dynamic visualization of local protein synthesis in hippocampal neurons.
2001, Pubmed
Aakalu,
Dynamic visualization of local protein synthesis in hippocampal neurons.
2001,
Pubmed
Antar,
Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses.
2006,
Pubmed
Arnaud,
Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development.
2003,
Pubmed
Bassell,
Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function.
2008,
Pubmed
Bassell,
Sorting of beta-actin mRNA and protein to neurites and growth cones in culture.
1998,
Pubmed
Bassell,
Binding proteins for mRNA localization and local translation, and their dysfunction in genetic neurological disease.
2004,
Pubmed
Bramham,
Dendritic mRNA: transport, translation and function.
2007,
Pubmed
Bureau,
Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice.
2008,
Pubmed
Campbell,
Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation.
2001,
Pubmed
,
Xenbase
Dahm,
Cell biology: silenced RNA on the move.
2005,
Pubmed
Eom,
Localization of a beta-actin messenger ribonucleoprotein complex with zipcode-binding protein modulates the density of dendritic filopodia and filopodial synapses.
2003,
Pubmed
Farina,
Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment.
2003,
Pubmed
Guirland,
Direct cAMP signaling through G-protein-coupled receptors mediates growth cone attraction induced by pituitary adenylate cyclase-activating polypeptide.
2003,
Pubmed
,
Xenbase
Hengst,
Functional and selective RNA interference in developing axons and growth cones.
2006,
Pubmed
Hüttelmaier,
Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1.
2005,
Pubmed
Kiebler,
Neuronal RNA granules: movers and makers.
2006,
Pubmed
Leung,
Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1.
2006,
Pubmed
,
Xenbase
Li,
Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A.
2009,
Pubmed
Lin,
Local translation and directional steering in axons.
2007,
Pubmed
Lin,
Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development.
2009,
Pubmed
,
Xenbase
Martin,
mRNA localization: gene expression in the spatial dimension.
2009,
Pubmed
Murashov,
RNAi pathway is functional in peripheral nerve axons.
2007,
Pubmed
Narayanan,
S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade.
2008,
Pubmed
Narayanan,
FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A.
2007,
Pubmed
Nielsen,
A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development.
1999,
Pubmed
,
Xenbase
Piper,
RNA translation in axons.
2004,
Pubmed
Price,
The RNA binding and transport proteins staufen and fragile X mental retardation protein are expressed by rat primary afferent neurons and localize to peripheral and central axons.
2006,
Pubmed
Richter,
CPEB: a life in translation.
2007,
Pubmed
,
Xenbase
Ross,
Characterization of a beta-actin mRNA zipcode-binding protein.
1997,
Pubmed
Santangelo,
Single molecule-sensitive probes for imaging RNA in live cells.
2009,
Pubmed
Sasaki,
Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex.
2002,
Pubmed
Steward,
Protein synthesis at synaptic sites on dendrites.
2001,
Pubmed
Sutton,
Dendritic protein synthesis, synaptic plasticity, and memory.
2006,
Pubmed
Tiruchinapalli,
Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons.
2003,
Pubmed
Wen,
BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.
2007,
Pubmed
,
Xenbase
Yao,
An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance.
2006,
Pubmed
,
Xenbase
Yisraeli,
VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins.
2005,
Pubmed
Zhang,
Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility.
2001,
Pubmed
Zheng,
Turning of nerve growth cones induced by neurotransmitters.
1994,
Pubmed
,
Xenbase
