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Dystrophin Dp71f associates with the beta1-integrin adhesion complex to modulate PC12 cell adhesion.

Abstract : Dystrophin Dp71 is the main product of the Duchenne muscular dystrophy gene in the brain; however, its function is unknown. To study the role of Dp71 in neuronal cells, we previously generated by antisense treatment PC12 neuronal cell clones with decreased Dp71 expression (antisense-Dp71 cells). PC12 cells express two different splicing isoforms of Dp71, a cytoplasmic variant called Dp71f and a nuclear isoform called Dp71d. We previously reported that antisense-Dp71 cells display deficient adhesion to substrate and reduced immunostaining of beta1-integrin in the cell area contacting the substrate. In this study, we isolated additional antisense-Dp71 clones to analyze in detail the potential involvement of Dp71f isoform with the beta1-integrin adhesion system of PC12 cells. Immunofluorescence analyses as well as immunoprecipitation assays demonstrated that the PC12 cell beta1-integrin adhesion complex is composed of beta1-integrin, talin, paxillin, alpha-actinin, FAK and actin. In addition, our results showed that Dp71f associates with most of the beta1-integrin complex components (beta1-integrin, FAK, alpha-actinin, talin and actin). In the antisense-Dp71 cells, the deficiency of Dp71 provokes a significant reduction of the beta1-integrin adhesion complex and, consequently, the deficient adhesion of these cells to laminin. In vitro binding experiments confirmed the interaction of Dp71f with FAK and beta1-integrin. Our data indicate that Dp71f is a structural component of the beta1-integrin adhesion complex of PC12 cells that modulates PC12 cell adhesion by conferring proper complex assembly and/or maintenance.
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https://www.hal.inserm.fr/inserm-00146212
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Submitted on : Tuesday, May 15, 2007 - 3:06:33 PM
Last modification on : Friday, March 27, 2020 - 9:20:05 AM
Long-term archiving on: : Wednesday, April 7, 2010 - 2:18:21 AM

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Joel Cerna, Doris Cerecedo, Arturo Ortega, Francisco García-Sierra, Federico Centeno, et al.. Dystrophin Dp71f associates with the beta1-integrin adhesion complex to modulate PC12 cell adhesion.. Journal of Molecular Biology, Elsevier, 2006, 362 (5), pp.954-65. ⟨10.1016/j.jmb.2006.07.075⟩. ⟨inserm-00146212⟩

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