Dystrophin Dp71 is required for neurite outgrowth in PC12 cells.
To determine the role of Dp71 in neuronal cells, we generated PC12 cell lines in which Dp71 protein levels were controlled by stable transfection with either antisense or sense constructs. Cells expressing the antisense Dp71 RNA (antisense-Dp71 cells) contained reduced amounts of the two endogenous Dp71 isoforms. Antisense-Dp71 cells exhibited a marked suppression of neurite outgrowth upon the induction with NGF or dibutyryl cyclic AMP. Early responses to NGF-induced neuronal differentiation, such as the cessation of cell division and the activation of ERK1/2 proteins, were normal in the antisense-Dp71 cells. On contrary, the induction of MAP2, a late differentiation marker, was disturbed in these cells. Additionally, the deficiency of Dp71 correlated with an altered expression of the dystrophin-associated protein complex (DAPC) members alpha and beta dystrobrevins. Our results indicate that normal expression of Dp71 is essential for neurite outgrowth in PC12 cells and constitute the first direct evidence implicating Dp71 in a neuronal function.
Acosta
Rosalinda
R
Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, Apartado Postal 14-740, C.P. 07000, Mexico D.F., Mexico.
Montañez
Cecilia
C
Fuentes-Mera
Lizeth
L
Gonzalez
Everardo
E
Gómez
Pablo
P
Quintero-Mora
Leonor
L
Mornet
Dominique
D
Alvarez-Salas
Luis M
LM
Cisneros
Bulmaro
B
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D016373:DNA, Antisense / Q000494:pharmacology; D016189:Dystrophin / Q000031:analogs & derivatives* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000032:analysis; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016501:Neurites / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology / Q000648:ultrastructure; D009479:Neuropeptides / Q000032:analysis; D016716:PC12 Cells / Q000166:cytology*; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D014162:Transfection
D016373:DNA, Antisense; D016189:Dystrophin; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; C085339:apo-dystrophin 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases