title: Regulation of neuronal differentiation by proteins associated with nuclear bodies.
abstract: Nuclear bodies are large sub-nuclear structures composed of RNA and protein molecules. The Survival of Motor Neuron (SMN) protein localizes to Cajal bodies (CBs) and nuclear gems. Diminished cellular concentration of SMN is associated with the neurodegenerative disease Spinal Muscular Atrophy (SMA). How nuclear body architecture and its structural components influence neuronal differentiation remains elusive. In this study, we analyzed the effects of SMN and two of its interaction partners in cellular models of neuronal differentiation. The nuclear 23 kDa isoform of Fibroblast Growth Factor - 2 (FGF-2(23)) is one of these interacting proteins - and was previously observed to influence nuclear bodies by destabilizing nuclear gems and mobilizing SMN from Cajal bodies (CBs). Here we demonstrate that FGF-2(23) blocks SMN-promoted neurite outgrowth, and also show that SMN disrupts FGF-2(23)-dependent transcription. Our results indicate that FGF-2(23) and SMN form an inactive complex that interferes with neuronal differentiation by mutually antagonizing nuclear functions. Coilin is another nuclear SMN binding partner and a marker protein for Cajal bodies (CBs). In addition, coilin is essential for CB function in maturation of small nuclear ribonucleoprotein particles (snRNPs). The role of coilin outside of Cajal bodies and its putative impacts in tissue differentiation are poorly defined. The present study shows that protein levels of nucleoplasmic coilin outside of CBs decrease during neuronal differentiation. Overexpression of coilin has an inhibitory effect on neurite outgrowth. Furthermore, we find that nucleoplasmic coilin inhibits neurite outgrowth independent of SMN binding revealing a new function for coilin in neuronal differentiation.
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Förthmann
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergeijk
authors.affiliation: Department of Pathology and Anatomical Sciences, State University of New York, Buffalo, New York, United States of America.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Lübben
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schill
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Hella
authors.initials: H
authors.lastname: Brinkmann
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ratzka
authors.affiliation: Department of Pathology and Anatomical Sciences, State University of New York, Buffalo, New York, United States of America.
authors.forename: Michal K
authors.initials: MK
authors.lastname: Stachowiak
authors.affiliation: Department of Biochemistry, The University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Hebert
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Claus
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D020541:Coiled Bodies / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D055532:SMN Complex Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; D055532:SMN Complex Proteins; D016222:Fibroblast Growth Factor 2; C068921:p80-coilin