Telethonin protein expression in neuromuscular disorders.
Telethonin is a 19-kDa sarcomeric protein, localized to the Z-disc of skeletal and cardiac muscles. Mutations in the telethonin gene cause limb-girdle muscular dystrophy type 2G (LGMD2G). We investigated the sarcomeric integrity of muscle fibers in LGMD2G patients, through double immunofluorescence analysis for telethonin with three sarcomeric proteins: titin, alpha-actinin-2, and myotilin and observed the typical cross striation pattern, suggesting that the Z-line of the sarcomere is apparently preserved, despite the absence of telethonin. Ultrastructural analysis confirmed the integrity of the sarcomeric architecture. The possible interaction of telethonin with other proteins responsible for several forms of neuromuscular disorders was also analyzed. Telethonin was clearly present in the rods in nemaline myopathy (NM) muscle fibers, confirming its localization to the Z-line of the sarcomere. Muscle from patients with absent telethonin showed normal expression for the proteins dystrophin, sarcoglycans, dysferlin, and calpain-3. Additionally, telethonin showed normal localization in muscle biopsies from patients with LGMD2A, LGMD2B, sarcoglycanopathies, and Duchenne muscular dystrophy (DMD). Therefore, the primary deficiency of calpain-3, dysferlin, sarcoglycans, and dystrophin do not seem to alter telethonin expression.
Vainzof
Mariz
M
Center for the Study of the Human Genome, Department Biology, IBUSP, University of Sao Paulo, R. do Matão, 277, sala 220-Cidade Universitária, São Paulo, Brazil. mvainzof@usp.br
Moreira
Eloisa S
ES
Suzuki
Oscar T
OT
Faulkner
Georgine
G
Valle
Georgio
G
Beggs
Alan H
AH
Carpen
Olli
O
Ribeiro
Alberto F
AF
Zanoteli
Edmar
E
Gurgel-Gianneti
Juliana
J
Tsanaclis
Ana Maria
AM
Silva
Helga C A
HC
Passos-Bueno
Maria Rita
MR
Zatz
Mayana
M
D000185:Actinin / Q000032:analysis; D001706:Biopsy; D064211:Connectin; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D008840:Microfilament Proteins; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000235:genetics; D009136:Muscular Dystrophies / Q000235:genetics; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics; D009154:Mutation; D017696:Myopathies, Nemaline / Q000235:genetics; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism
C401401:ACTN2 protein, human; D064211:Connectin; D003598:Cytoskeletal Proteins; C577290:MYOT protein, human; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C577292:TCAP protein, human; D000185:Actinin