Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

Dilek Colak; Sheng-Jian Ji; Bo T Porse; Samie R Jaffrey

doi:10.1016/j.cell.2013.04.056

Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

Dilek Colak, Sheng-Jian Ji, Bo T Porse, Samie R Jaffrey

Institut for Klinisk Medicin

117 Citationer (Scopus)

Abstract

Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	153
Udgave nummer	6
Sider (fra-til)	1252-65
Antal sider	14
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2013.04.056
Status	Udgivet - 6 jun. 2013

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10.1016/j.cell.2013.04.056

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@article{10d9223886af4871938903379df96fc1,

title = "Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay",

abstract = "Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.",

keywords = "Animals, Axons, Embryo, Mammalian, Growth Cones, Membrane Proteins, Mice, Nerve Tissue Proteins, Neurons, Nonsense Mediated mRNA Decay, Protein Biosynthesis, RNA Isoforms, RNA Stability, Spinal Cord",

author = "Dilek Colak and Sheng-Jian Ji and Porse, {Bo T} and Jaffrey, {Samie R}",

year = "2013",

month = jun,

day = "6",

doi = "10.1016/j.cell.2013.04.056",

language = "English",

volume = "153",

pages = "1252--65",

journal = "Cell",

issn = "0092-8674",

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TY - JOUR

T1 - Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

AU - Colak, Dilek

AU - Ji, Sheng-Jian

AU - Porse, Bo T

AU - Jaffrey, Samie R

PY - 2013/6/6

Y1 - 2013/6/6

N2 - Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.

AB - Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.

KW - Animals

KW - Axons

KW - Embryo, Mammalian

KW - Growth Cones

KW - Membrane Proteins

KW - Mice

KW - Nerve Tissue Proteins

KW - Neurons

KW - Nonsense Mediated mRNA Decay

KW - Protein Biosynthesis

KW - RNA Isoforms

KW - RNA Stability

KW - Spinal Cord

U2 - 10.1016/j.cell.2013.04.056

DO - 10.1016/j.cell.2013.04.056

M3 - Journal article

C2 - 23746841

SN - 0092-8674

VL - 153

SP - 1252

EP - 1265

JO - Cell

JF - Cell

IS - 6

ER -

Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

Abstract

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