Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein.
During development, axon growth rates are precisely regulated to provide temporal control over pathfinding. The precise temporal regulation of axonal growth is a key step in the formation of functional synapses and the proper patterning of the nervous system. The rate of axonal elongation is increased by factors such as netrin-1 and nerve growth factor (NGF), which stimulate axon outgrowth using incompletely defined pathways. To clarify the mechanism of netrin-1- and NGF-stimulated axon growth, we explored the role of local protein translation. We found that intra-axonal protein translation is required for stimulated, but not basal, axon outgrowth. To identify the mechanism of translation-dependent outgrowth, we examined the PAR complex, a cytoskeleton regulator. We found that the PAR complex, like local translation, is required for stimulated, but not basal, outgrowth. Par3 mRNA is localized to developing axons, and NGF and netrin-1 trigger its local translation. Selective ablation of Par3 mRNA from axons abolishes the outgrowth-promoting effect of NGF. These results identify a new role for local translation and the PAR complex in axonal outgrowth.
Hengst
Ulrich
U
Department of Pharmacology, Weill Medical College, Cornell University, NY 10065, USA.
Deglincerti
Alessia
A
Kim
Hyung Joon
HJ
Jeon
Noo Li
NL
Jaffrey
Samie R
SR
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation; D016764:Cell Polarity; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D015870:Gene Expression / Q000187:drug effects; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617354:Ntn1 protein, rat; C472451:Pard3 protein, rat; C504908:Pard6a protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D020932:Nerve Growth Factor; C115015:PKC-3 protein; D011493:Protein Kinase C