PUBLICATION
The Heterogeneous Nuclear Ribonucleoprotein R is Necessary for Axonal {beta}-actin mRNA Translocation in Spinal Motor neurons
- Authors
- Glinka, M., Herrmann, T., Funk, N., Havlicek, S., Rossoll, W., Winkler, C., and Sendtner, M.
- ID
- ZDB-PUB-100223-48
- 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.
Citation
Glinka, M., Herrmann, T., Funk, N., Havlicek, S., Rossoll, W., Winkler, C., and Sendtner, M. (2010) The Heterogeneous Nuclear Ribonucleoprotein R is Necessary for Axonal {beta}-actin mRNA Translocation in Spinal Motor neurons. Human molecular genetics. 19(10):1951-1966.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping