ZFIN ID: ZDB-PUB-100223-48
The Heterogeneous Nuclear Ribonucleoprotein R is Necessary for Axonal {beta}-actin mRNA Translocation in Spinal Motor neurons
Glinka, M., Herrmann, T., Funk, N., Havlicek, S., Rossoll, W., Winkler, C., and Sendtner, M.
Date: 2010
Source: Human molecular genetics   19(10): 1951-1966 (Journal)
Registered Authors: Winkler, Christoph
Keywords: none
MeSH Terms:
  • 3' Untranslated Regions/genetics
  • Actins/genetics
  • Actins/metabolism*
  • Animals
  • Axons/metabolism*
  • Axons/pathology
  • Calcium Channels, N-Type/metabolism
  • Cell Separation
  • Embryo, Nonmammalian/pathology
  • Gene Knockdown Techniques
  • Growth Cones/metabolism
  • Heterogeneous-Nuclear Ribonucleoproteins/genetics
  • Heterogeneous-Nuclear Ribonucleoproteins/metabolism*
  • Mice
  • Motor Neurons/metabolism*
  • Motor Neurons/pathology
  • Protein Binding
  • RNA Transport*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • RNA, Small Interfering/metabolism
  • Spine/metabolism*
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
PubMed: 20167579 Full text @ Hum. Mol. Genet.
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ABSTRACT
Axonal transport and translation of beta-actin mRNA plays an important role for axonal growth and presynaptic differentiation in many neurons including hippocampal, cortical and spinal motor neurons. Several beta-actin mRNA binding and transport proteins have been identified, among them ZBP1, ZBP2 and hnRNP-R. HnRNP-R has been identified as an interaction partner of the survival motor neuron protein that is deficient in spinal muscular atrophy. Little is known about the function of hnRNP-R in axonal beta-actin translocation. We studied the role of hnRNP-R in motor neurons by knockdown in zebrafish embryos and isolated mouse motor neurons. HnRNP-R and beta-actin mRNA are colocalized in axons. Recombinant hnRNP-R interacts directly with the 3'UTR of beta-actin mRNA. Suppression of hnRNP-R in developing zebrafish embryos results in reduced axon growth in spinal motor neurons, without any alteration in motor neuron survival. ShRNA-mediated knockdown in isolated embryonic mouse motor neurons reduces beta-actin mRNA translocation to the axonal growth cone, which is paralleled by reduced axon elongation. Dendrite growth and neuronal survival were not affected by hnRNP-R depletion in these neurons. The loss of beta-actin mRNA in axonal growth cones of hnRNP-R depleted motor neurons resembles that observed in Smn-deficient motor neurons, a model for the human disease spinal muscular atrophy. In particular, hnRNP-R-depleted motor neurons also exhibit defects in presynaptic clustering of voltage-gated calcium channels. Our data suggest that hnRNP-R-mediated axonal beta-actin mRNA translocation plays an essential physiological role for axon growth and presynaptic differentiation.
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