title: Immobile survival of motoneuron (SMN) protein stored in Cajal bodies can be mobilized by protein interactions.
abstract: Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-2(23)) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-2(23) depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-2(23) accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-2(23) caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-2(23), leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly.
authors: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, Germany.
authors: Benjamin
authors: B
authors: Förthmann
authors: Hella
authors: H
authors: Brinkmann
authors: Andreas
authors: A
authors: Ratzka
authors: Michal K
authors: MK
authors: Stachowiak
authors: Claudia
authors: C
authors: Grothe
authors: Peter
authors: P
authors: Claus
mesh_terms: D020541:Coiled Bodies / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D057809:HEK293 Cells; D006801:Humans; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D020033:Protein Isoforms / Q000378:metabolism; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D020033:Protein Isoforms; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D055532:SMN Complex Proteins; D016222:Fibroblast Growth Factor 2; C068921:p80-coilin