title: The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal beta-actin mRNA translocation in spinal motor neurons.
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, 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 beta-actin translocation. hnRNP-R and beta-actin mRNA are colocalized in axons. Recombinant hnRNP-R interacts directly with the 3'-UTR of beta-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 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.
authors.affiliation: Institute for Clinical Neurobiology, Zinklesweg 10, 97078 Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Glinka
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.forename: Natalja
authors.initials: N
authors.lastname: Funk
authors.forename: Steven
authors.initials: S
authors.lastname: Havlicek
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rossoll
authors.forename: Christoph
authors.initials: C
authors.lastname: Winkler
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002469:Cell Separation; D004625:Embryo, Nonmammalian / Q000473:pathology; D055785:Gene Knockdown Techniques; D020439:Growth Cones / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013131:Spine / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; C500963:Cacna1b protein, mouse; D020864:Calcium Channels, N-Type; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C486686:Hnrpr protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D029961:Zebrafish Proteins; C550916:hnrnpr protein, zebrafish