title: The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus.
abstract: Spinal muscular atrophy is a neurodegenerative disease accompanied by a loss of motoneurons. Either mutations or deletions in the survival of motoneuron (SMN) gene are responsible for this defect. SMN is an assembly protein for RNA-protein complexes in the nucleus and is also found in axons of neurons. However, it is unclear which dysfunctions of SMN are important for disease progression. In this study we analyzed the contributions of different SMN regions for localization and neuronal differentiation associated with outgrowth of neurites. Suppression of endogenous SMN protein levels significantly decreased the growth of neurites. Down-regulation of the interacting protein gemin2 had the opposite effect. Surprisingly, selective overexpression of the SMN C-terminal domain promoted neurite outgrowth similar to full-length protein and could rescue the SMN knock-down effects. The knock-down led to a significant change in the G-/F-actin ratio, indicating a role for SMN in actin dynamics. Therefore, our data suggest a functional role for SMN in microfilament metabolism in axons of motoneurons.
authors.affiliation: Department of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergeijk
authors.forename: Katharina
authors.initials: K
authors.lastname: Rydel-Könecke
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
authors.forename: Peter
authors.initials: P
authors.lastname: Claus
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016501:Neurites; D016716:PC12 Cells; D011485:Protein Binding; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
chemical_list: D000199:Actins; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein