Partial deletion of the MAPT gene: a novel mechanism of FTDP-17.
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.
Rovelet-Lecrux
Anne
A
Inserm U614, Faculty of medicine, 76183, Rouen, France.
Lecourtois
Magalie
M
Thomas-Anterion
Catherine
C
Le Ber
Isabelle
I
Brice
Alexis
A
Frebourg
Thierry
T
Hannequin
Didier
D
Campion
Dominique
D
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
C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D016875:tau Proteins