title: Myotonic dystrophy type 1-associated CTG repeats disturb the expression and subcellular distribution of microtubule-associated proteins MAP1A, MAP2, and MAP6/STOP in PC12 cells.
abstract: To study the effect of DM1-associated CTG repeats on neuronal function, we developed a PC12 cell-based model that constitutively expresses the DMPK gene 3'-untranslated region with 90 CTG repeats (CTG90 cells). As CTG90 cells exhibit impaired neurite outgrowth and as microtubule-associated proteins (MAPs) are crucial for microtubule stability, we analyzed whether MAPs are a target of CTG repeats. NGF induces mRNA expression of Map2, Map1a and Map6 in control cells (PC12 cells transfected with the empty vector), but this induction is abolished for Map2 and Map1a in CTG90 cells. MAP2 and MAP6/STOP proteins decrease in NGF-treated CTG90 cells, whereas MAP1A increases. Data suggest that CTG repeats might alter somehow the expression of MAPs, which appears to be related with CTG90 cell-deficient neurite outgrowth. Decreased MAP2 levels found in the hippocampus of a DM1 mouse model indicates that targeting of MAPs expression by CTG repeats might be relevant to DM1.
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico, DF, Mexico.
authors.forename: Prisiliana
authors.initials: P
authors.lastname: Velázquez-Bernardino
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Sierra
authors.forename: Oscar
authors.initials: O
authors.lastname: Hernández-Hernández
authors.forename: Mario
authors.initials: M
authors.lastname: Bermúdez de León
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gourdon
authors.forename: Mário
authors.initials: M
authors.lastname: Gomes-Pereira
authors.forename: Bulmaro
authors.initials: B
authors.lastname: Cisneros
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000473:pathology; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D016501:Neurites / Q000473:pathology; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018911:Trinucleotide Repeats / Q000235:genetics / Q000502:physiology*
chemical_list: C585516:DMPK protein, mouse; C489787:MAP2 protein, rat; C490546:Map1a protein, rat; C113727:Map6 protein, rat; D008869:Microtubule-Associated Proteins; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases