title: Partial deletion of the MAPT gene: a novel mechanism of FTDP-17.
abstract: A heterozygous genomic deletion removing exons 6 to 9 of the microtubule associated protein tau (MAPT) gene, predicting to result into a truncated protein lacking the first microtubule binding domain, was detected in a patient with frontotemporal dementia (FTD). Cell culture experiments showed that the truncated tau isoforms had a dramatic decrease in the normal binding to microtubules but acquired the ability to bind microtubule associated protein-1B (MAP-1B). This indicates that this tauopathy likely results both from a loss of function mechanism and from a deleterious gain of function by which cytoplasmic deleted forms of tau sequester another MAP. Both mechanisms could contribute to impair microtubule dynamics.
authors.affiliation: Inserm U614, Faculty of medicine, 76183, Rouen, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Rovelet-Lecrux
authors.forename: Magalie
authors.initials: M
authors.lastname: Lecourtois
authors.forename: Catherine
authors.initials: C
authors.lastname: Thomas-Anterion
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D017353:Gene Deletion; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D024801:Tauopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D016875:tau Proteins