Dysferlin is a plasma membrane protein and is expressed early in human development

Details

Serval ID
serval:BIB_A1D9FAE797B8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dysferlin is a plasma membrane protein and is expressed early in human development
Journal
Human Molecular Genetics
Author(s)
Anderson  L. V., Davison  K., Moss  J. A., Young  C., Cullen  M. J., Walsh  J., Johnson  M. A., Bashir  R., Britton  S., Keers  S., Argov  Z., Mahjneh  I., Fougerousse  F., Beckmann  J. S., Bushby  K. M.
ISSN
0964-6906 (Print)
Publication state
Published
Issued date
05/1999
Volume
8
Number
5
Pages
855-61
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Abstract
Recently, a single gene, DYSF, has been identified which is mutated in patients with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy (MM). This is of interest because these diseases have been considered as two distinct clinical conditions since different muscle groups are the initial targets. Dysferlin, the protein product of the gene, is a novel molecule without homology to any known mammalian protein. We have now raised a monoclonal antibody to dysferlin and report on the expression of this new protein: immunolabelling with the antibody (designated NCL-hamlet) demonstrated a polypeptide of approximately 230 kDa on western blots of skeletal muscle, with localization to the muscle fibre membrane by microscopy at both the light and electron microscopic level. A specific loss of dysferlin labelling was observed in patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two different frameshifting mutations demonstrated very low levels of immunoreactive protein in a manner reminiscent of the dystrophin expressed in many Duchenne patients. Analysis of human fetal tissue showed that dysferlin was expressed at the earliest stages of development examined, at Carnegie stage 15 or 16 (embryonic age 5-6 weeks). Dysferlin is present, therefore, at a time when the limbs start to show regional differentiation. Lack of dysferlin at this critical time may contribute to the pattern of muscle involvement that develops later, with the onset of a muscular dystrophy primarily affecting proximal or distal muscles.
Keywords
Amino Acid Sequence Animals Antibodies, Monoclonal/metabolism Cell Membrane/*metabolism Extremities/*embryology *Gene Expression Regulation, Developmental Humans *Membrane Proteins Molecular Sequence Data Muscle Proteins/*genetics/immunology/*metabolism Muscle, Skeletal/metabolism Muscular Dystrophies/genetics/metabolism Rats
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 16:17
Last modification date
20/08/2019 15:07
Usage data