RT Journal Article
SR Electronic
T1 Palladin Is a Neuron-Specific Translational Target of mTOR Signaling That Regulates Axon Morphogenesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4985
OP 4995
DO 10.1523/JNEUROSCI.2370-17.2018
VO 38
IS 21
A1 Yusuke Umegaki
A1 Antonio Martínez Brotons
A1 Yui Nakanishi
A1 Zhongyue Luo
A1 Hanlu Zhang
A1 Azad Bonni
A1 Yoshiho Ikeuchi
YR 2018
UL http://www.jneurosci.org/content/38/21/4985.abstract
AB The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates neuronal morphogenesis downstream of mTOR signaling. Our findings provide novel insights into an mTOR-dependent mechanism that controls neuronal morphogenesis through translational regulation.SIGNIFICANCE STATEMENT This study reports the discovery of neuron-specific protein translational responses to alterations of mTOR activity. By using ribosome profiling analysis, which can reveal the location and quantity of translating ribosomes on mRNAs, multiple aspects of protein translation were quantitatively analyzed in mouse embryonic stem cells and cortical neurons upon acute mTOR inhibition. Neurons displayed distinct patterns of ribosome occupancy for each codon and ribosome stalling during translation at specific positions of mRNAs. Importantly, the cytoskeletal regulator palladin was identified as a translational target protein of mTOR signaling in neurons. Palladin operates downstream of mTOR to modulate axon morphogenesis. This study identifies a novel mechanism of neuronal morphogenesis regulated by mTOR signaling through control of translation of the key protein palladin.