title: PPP4R2 regulates neuronal cell differentiation and survival, functionally cooperating with SMN.
abstract: Spinal muscular atrophy (SMA) is a human disease caused by reduced levels of the Survival of Motor Neuron (SMN) protein, leading to progressive loss of motor neurons and muscular paralysis. However, it is still not very clear why these cells are specifically sensitive to SMN levels. Therefore, understanding which proteins may functionally interact with SMN in a neuronal context is a very important issue. PPP4R2, a regulatory subunit of the protein phosphatase 4 (PPP4C), was previously identified as a functional interactor of the SMN complex, but has never been studied in neuronal cells. In this report, we show that PPP4R2 displays a very dynamic intracellular localization in mouse and rat neuronal cell lines and in rat primary hippocampal neurons, strongly correlating with differentiation. More importantly, we found that PPP4R2 loss of function impairs the differentiation of the mouse motor-neuronal cell line NSC-34, an effect that can be counteracted by SMN overexpression. In addition, we show that PPP4R2 may specifically protect NSC-34 cells from DNA damage-induced apoptosis and that it is capable to functionally cooperate with SMN in this activity. Our data indicate that PPP4R2 is a SMN partner that may modulate the differentiation and survival of neuronal cells.
authors.affiliation: Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Italy.
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Bosio
authors.forename: Gaia
authors.initials: G
authors.lastname: Berto
authors.forename: Paola
authors.initials: P
authors.lastname: Camera
authors.forename: Federico
authors.initials: F
authors.lastname: Bianchi
authors.forename: Chiara
authors.initials: C
authors.lastname: Ambrogio
authors.forename: Peter
authors.initials: P
authors.lastname: Claus
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002470:Cell Survival; D004249:DNA Damage; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D051381:Rats; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C526472:Smn1 protein, mouse; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; D049452:Green Fluorescent Proteins; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4