The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal β-actin mRNA translocation in spinal motor neurons

Michael Glinka, Thomas Herrmann, Natalja Funk, Steven Havlicek, Wilfried Rossoll, Christoph Winkler, Michael Sendtner

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Axonal transport and translation of β-actin mRNA plays an important role for axonal growth and presynaptic differentiation in many neurons including hippocampal, cortical and spinal motor neurons. Several β-actin mRNA-binding and transport proteins have been identified, including ZBP1, ZBP2 and hnRNP-R. hnRNP-R has been found 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 β-actin translocation. hnRNP-R and β-actin mRNA are colocalized in axons. Recombinant hnRNP-R interacts directly with the 3′-UTR of β-actin mRNA. We studied the role of hnRNP-R in motor neurons by knockdown in zebrafish embryos and isolated mouse motor neurons. 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 β-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 β-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 β-actin mRNA translocation plays an essential physiological role for axon growth and presynaptic differentiation.

Original languageEnglish (US)
Pages (from-to)1951-1966
Number of pages16
JournalHuman molecular genetics
Volume19
Issue number10
DOIs
StatePublished - Feb 18 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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