Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein.
Mutations in genes encoding for the sarcoglycans, a subset of proteins within the dystrophin-glycoprotein complex, produce a limb-girdle muscular dystrophy phenotype; however, the precise role of this group of proteins in the skeletal muscle is not known. To understand the role of the sarcoglycan complex, we looked for sarcoglycan interacting proteins with the hope of finding novel members of the dystrophin-glycoprotein complex. Using the yeast two-hybrid method, we have identified a skeletal muscle-specific form of filamin, which we term filamin 2 (FLN2), as a gamma- and delta-sarcoglycan interacting protein. In addition, we demonstrate that FLN2 protein localization in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patients and mice is altered when compared with unaffected individuals. Previous studies of filamin family members have determined that these proteins are involved in actin reorganization and signal transduction cascades associated with cell migration, adhesion, differentiation, force transduction, and survival. Specifically, filamin proteins have been found essential in maintaining membrane integrity during force application. The finding that FLN2 interacts with the sarcoglycans introduces new implications for the pathogenesis of muscular dystrophy.
Thompson
T G
TG
Howard Hughes Medical Institute and Division of Genetics, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Chan
Y M
YM
Hack
A A
AA
Brosius
M
M
Rajala
M
M
Lidov
H G
HG
McNally
E M
EM
Watkins
S
S
Kunkel
L M
LM
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003285:Contractile Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D049030:Dystroglycans; D064448:Filamins; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012441:Saccharomyces cerevisiae; D049031:Sarcoglycans; D017386:Sequence Homology, Amino Acid
D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; C578661:FLNC protein, human; D064448:Filamins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D020033:Protein Isoforms; D049031:Sarcoglycans; D049030:Dystroglycans