Indications for a novel muscular dystrophy pathway:: γ-filamin, the muscle-specific filamin isoform, interacts with myotilin

被引:154
作者
van der Ven, PFM
Wiesner, S
Salmikangas, P
Auerbach, D
Himmel, M
Kempa, S
Hayess, K
Pacholsky, D
Taivainen, A
Schröder, R
Carpén, O
Fürst, DO
机构
[1] Univ Potsdam, Dept Cell Biol, D-14471 Potsdam, Germany
[2] Univ Helsinki, Haartman Inst, Dept Pathol, SF-00290 Helsinki, Finland
[3] ETH Zurich, Inst Cell Biol, CH-8093 Zurich, Switzerland
[4] Univ Hosp Bonn, Dept Neurol, D-53127 Bonn, Germany
关键词
filamin; myotilin; limb-girdle muscular dystrophy; myofibrils; Z-disc proteins;
D O I
10.1083/jcb.151.2.235
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
gamma -Filamin, also called ABP-L, is a filamin isororm that is specifically expressed in striated muscles, where it is predominantly localized in myofibrillar Z-discs. A minor fraction of the protein shows subsarcolemmal localization. Although gamma -filamin has the same overall structure as the two other known isoforms, it is the only isoform that carries a unique insertion in its immunoglobulin (Ig)-like domain 20. Sequencing of the genomic region encoding this part of the molecule shows that this insert is encoded by an extra exon. Transient transfections of the insert-bearing domain in skeletal muscle cells and cardiomyocytes show that this single domain is sufficient for targeting to developing and mature Z-discs. The yeast two-hybrid method was used to identify possible binding partners for the insert-bearing Ig-like domain 20 of gamma -filamin. The two Ig-like domains of the recently described alpha -actinin-binding Z-disc protein myotilin were found to interact directly with this filamin domain, indicating that the amino-terminal end of gamma -filamin may be indirectly anchored to alpha -actinin in the Z-disc via myotilin. Since defects in the myotilin gene were recently reported to cause a form of autosomal dominant limb-girdle muscular dystrophy, our findings provide a further contribution to the molecular understanding of this disease.
引用
收藏
页码:235 / 247
页数:13
相关论文
共 66 条
  • [11] FRANZINIARMSTRO.C, 1994, MYOLOGY, P74
  • [12] THE ORGANIZATION OF TITIN FILAMENTS IN THE HALF-SARCOMERE REVEALED BY MONOCLONAL-ANTIBODIES IN IMMUNOELECTRON MICROSCOPY - A MAP OF 10 NONREPETITIVE EPITOPES STARTING AT THE Z-LINE EXTENDS CLOSE TO THE M-LINE
    FURST, DO
    OSBORN, M
    NAVE, R
    WEBER, K
    [J]. JOURNAL OF CELL BIOLOGY, 1988, 106 (05) : 1563 - 1572
  • [13] COMPARATIVE MAPPING OF THE ACTIN-BINDING PROTEIN-280 GENES IN HUMAN AND MOUSE
    GARIBOLDI, M
    MAESTRINI, E
    CANZIAN, F
    MANENTI, G
    DEGREGORIO, L
    RIVELLA, S
    CHATTERJEE, A
    HERMAN, GE
    ARCHIDIACONO, N
    ANTONACCI, R
    PIEROTTI, MA
    DRAGANI, TA
    TONIOLO, D
    [J]. GENOMICS, 1994, 21 (02) : 428 - 430
  • [14] THE SYNTHESIS AND DEPLOYMENT OF FILAMIN IN CHICKEN SKELETAL-MUSCLE
    GOMER, RH
    LAZARIDES, E
    [J]. CELL, 1981, 23 (02) : 524 - 532
  • [15] HIGHLY HOMOLOGOUS FILAMIN POLYPEPTIDES HAVE DIFFERENT DISTRIBUTIONS IN AVIAN SLOW AND FAST MUSCLE-FIBERS
    GOMER, RH
    LAZARIDES, E
    [J]. JOURNAL OF CELL BIOLOGY, 1983, 97 (03) : 818 - 823
  • [16] GONCHAROVA EJ, 1992, DEVELOPMENT, V114, P173
  • [17] HUMAN ENDOTHELIAL ACTIN-BINDING PROTEIN (ABP-280, NONMUSCLE FILAMIN) - A MOLECULAR LEAF SPRING
    GORLIN, JB
    YAMIN, R
    EGAN, S
    STEWART, M
    STOSSEL, TP
    KWIATKOWSKI, DJ
    HARTWIG, JH
    [J]. JOURNAL OF CELL BIOLOGY, 1990, 111 (03) : 1089 - 1105
  • [18] ACTIN-BINDING PROTEIN (ABP-280) FILAMIN GENE (FLN) MAPS TELOMERIC TO THE COLOR-VISION LOCUS (R/GCP) AND CENTROMERIC TO G6PD IN XQ28
    GORLIN, JB
    HENSKE, E
    WARREN, ST
    KUNST, CB
    DURSO, M
    PALMIERI, G
    HARTWIG, JH
    BRUNS, G
    KWIATKOWSKI, DJ
    [J]. GENOMICS, 1993, 17 (02) : 496 - 498
  • [19] Grönholm M, 1999, J CELL SCI, V112, P895
  • [20] Myotilin is mutated in limb girdle muscular dystrophy 1A
    Hauser, MA
    Horrigan, SK
    Salmikangas, P
    Torian, UM
    Viles, KD
    Dancel, R
    Tim, RW
    Taivainen, A
    Bartoloni, L
    Gilchrist, JM
    Stajich, JM
    Gaskell, PC
    Gilbert, JR
    Vance, JM
    Pericak-Vance, MA
    Carpen, O
    Westbrook, CA
    Speer, MC
    [J]. HUMAN MOLECULAR GENETICS, 2000, 9 (14) : 2141 - 2147