FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion.

S Yen; C Easson; P Nacharaju; M Hutton; S H Yen

doi:10.1016/s0014-5793(99)01427-1

Home/Archive/PubMed

PubMed · 10561502

FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion.

S Yen·C Easson·P Nacharaju·M Hutton·S H Yen

View original source ↗Export metadata ↓

Abstract

Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation.

Explore related subjects

Calpain Chromosomes, Human, Pair 17 Dementia Frontal Lobe Humans Immunoblotting Kinetics Mutation Parkinsonian Disorders Recombinant Proteins Silver Staining Time Factors tau Proteins Journal Article Research Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

S Yen, C Easson, P Nacharaju, M Hutton, S H Yen. 1999-11-12. FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion.. https://doi.org/10.1016/s0014-5793(99)01427-1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2001

Strategy for mutation analysis in the autosomal recessive limb-girdle muscular dystrophies.

We describe a strategy for molecular diagnosis in the autosomal recessive limb-girdle muscular dystrophies, a highly heterogeneous group of inherited muscle-wasting diseases. Genetic mutation analysis is directed by immunoanalysis of muscle biopsies using antibodies against a panel of muscular dystrophy-associated proteins. Performing the molecular analysis in this way greatly increases the chance that mutations will be found in the first gene examined. The use of this strategy can significantly decrease the time involved in determining the genetic fault in a patient with a clinical diagnosis of recessive limb-girdle muscular dystrophy, as well as having a feedback effect, which is useful in helping clinicians to identify subtle clinical differences between the subtypes of the disease. The use of this approach has so far helped us to identify mutations in ten sarcoglycanopathy (limb-girdle muscular dystrophy 2C-2F) patients, and seven calpainopathy (limb-girdle muscular dystrophy 2A) patients.

Calpain↗

PubMed2000

High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia.

Autosomal recessive limb gird muscular dystrophy (LGMD2) is a clinically and genetically heterogeneous group of diseases that are characterized by progressive atrophy and weakness of the proximal limb muscles. At least eight genetic loci leading to LGMD2 are recognized. The proportion of particular gene involved in producing different forms of LGMD2 shows a marked geographical variation. We studied 19 LGMD2 patients from Russia (15 families) and found calpain 3 (CAPN3) gene mutations in most of the patients studied. Sequence analysis of the fourth exons revealed two sibs - heterozygous compound for a 15-bp deletion (nt598-612) and 550 adenine deletion, and two sibs homozygous for a 550delA. We developed assay based on allele specific amplification (ASA) for rapid screening of the 550delA. The ASA assay of the LGMD2 patients under study showed that 7 patients from 6 families were homozygous for 550delA and 7 patients from 4 families were heterozygous for 550delA. A linkage analysis employing four microsatellites flanking the LGMD2A locus was performed. We found complete haplotype identity in most cases what favors the possibility of a common founder. Heterozygous carriers of 550delA were found in general population. The crude estimate of the mutation frequency is 1/150. Hum Mutat 15:295, 2000.

Calpain↗

PubMed2000

Unprecedented crystallization and X-ray crystal structure of racemic N(alpha)-(t-butyloxycarbonyl)-L-L-phenylalanine N-methoxy-N-methylamide.

Weinreb amide 3 was synthesized using isobutyl chloroformate, carbonyldiimidazole, or ethylcarbodiimide as the coupling agent in the reaction of Boc-phenylalanine with O,N-dimethylhydroxylamine hydrochloride. An optically active oil was isolated along with an optically inactive solid irrespective of the type of coupling agent used. Single crystal X-ray analysis of the solid revealed that it is a racemate. The molecular packing of the crystals reflect the stability of the racemate as opposed to an enantiomerically pure solid.

Calpain↗