@article{RaynaudJondNecandMarcilhacetal.2006, author = {Raynaud, F and Jond-Necand, C and Marcilhac, Anne and F{\"u}rst, Dieter Oswald and Benyamin, Yves}, title = {Calpain 1-gamma filamin interaction in muscle cells : a possible in situ regulation by PKC-alpha}, year = {2006}, language = {en} } @article{RaynaudJondNecandMarcilhacetal.2006, author = {Raynaud, F and Jond-Necand, C and Marcilhac, Anne and F{\"u}rst, Dieter Oswald and Benyamin, Yves}, title = {Calpain 1-gamma filamin interaction in muscle cells :a possible in situ regulation by PKC-alpha}, year = {2006}, language = {en} } @article{VanderVenEhlerVakeeletal.2006, author = {VanderVen, Peter F. M. and Ehler, Elisabeth and Vakeel, Padmanabhan and Eulitz, Stefan and Schenk, J{\"o}rg A. and Milting, Hendrik and Micheel, Burkhard and F{\"u}rst, Dieter Oswald}, title = {Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/ VASP}, doi = {10.1016/j.yexcr.2006.03.015}, year = {2006}, abstract = {Filamin c is the predominantly expressed filamin isoform in striated muscles. It is localized in myofibrillar Z- discs, where it binds FATZ and myotilin, and in myotendinous junctions and intercalated discs. Here, we identify Xin, the protein encoded by the human gene 'cardiomyopathy associated 1' (CMYA1) as filamin c binding partner at these specialized structures where the ends of myofibrils are attached to the sarcolemma. Xin directly binds the EVH1 domain proteins Mena and VASP. In the adult heart, Xin and Mena/VASP colocalize with filamin c in intercalated discs. In cultured cardiomyocytes, the proteins also localize in the nonstriated part of myofibrils, where sarcomeres are assembled and an extensive reorganization of the actin cytoskeleton occurs. Unusual intraexonic splicing events result in the existence of three Xin isoforms that associate differentially with its ligands. The identification of the complex filamin c-Xin-Mena/VASP provides a first glance on the role of Xin in the molecular mechanisms involved in developmental and adaptive remodeling of the actin cytoskeleton during cardiac morphogenesis and sarcomere assembly. (c) 2006 Elsevier Inc. All rights reserved}, language = {en} } @article{LangeHimmelAuerbachetal.2005, author = {Lange, Stephan and Himmel, Mirko and Auerbach, Daniel and Agarkova, Irina and Hayess, Katrin and F{\"u}rst, Dieter Oswald and Perriard, Jean-Claude and Ehler, Elisabeth}, title = {Dimerisation of myomesin : implications for the structure of the sarcomeric M-band}, issn = {0022-2836}, year = {2005}, abstract = {The sarcomeric M-band is thought to provide a link between the thick and the elastic, filament systems. So far, relatively little is known about its structural components and their three-dimensional organisation. Myomesin seems to be an essential component of the M-band, since it is expressed in all types of vertebrate striated muscle fibres investigated and can be found in its mature localisation pattern as soon as the first myofibrils are assembled. Previous work has shown that the N-terminal and central part of myomesin harbour binding sites for myosin, titin and muscle creatine kinase. Intrigued by the highly conserved domain layout of the C-terminal half, we screened for new interaction partners by yeast two-hybrid analysis. This revealed a strong interaction of myomesin with itself. This finding was confirmed by several biochemical assays. Our data suggest that myomesin can form antiparallel dimers via a binding site residing in its C-terminal domain 13. We suggest that, similar to alpha-actinin in the Z-disc, the myomesin dimers cross- link the contractile filaments in the M-band. The new and the already previously identified myomesin interaction sites are integrated into the first three-dimensional model of the sarcomeric M-band on a molecular basis. (C) 2004 Elsevier Ltd. All rights reserved}, language = {en} } @article{VorgerdvanderVenBruchertseiferetal.2005, author = {Vorgerd, M. and vanderVen, Peter F. M. and Bruchertseifer, V. and Lowe, T. and Kley, R. A. and Schr{\"o}der, Rolf and Lochmuller, H. and Himmel, Mirko and Koehler, K. and F{\"u}rst, Dieter Oswald and Huebner, A.}, title = {A mutation in the dimerization domain of filamin C causes a novel type of autosomal dominant myofibrillar myopathy}, issn = {0002-9297}, year = {2005}, abstract = {Myofibrillar myopathy (MFM) is a human disease that is characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations. In an extended German pedigree with a novel form of MFM characterized by clinical features of a limb-girdle myopathy and morphological features of MFM, we identified a cosegregating, heterozygous nonsense mutation (8130G -> A; W2710X) in the filamin c gene ( FLNC) on chromosome 7q32.1. The mutation is the first found in FLNC and is localized in the dimerization domain of filamin c. Functional studies showed that, in the truncated mutant protein, this domain has a disturbed secondary structure that leads to the inability to dimerize properly. As a consequence of this malfunction, the muscle fibers of our patients display massive cytoplasmic aggregates containing filamin c and several Z-disk-associated and sarcolemmal proteins}, language = {en} } @article{GehmlichGeierOsterzieletal.2004, author = {Gehmlich, Katja and Geier, C. and Osterziel, Karl Joseph and F{\"u}rst, Dieter Oswald}, title = {Mutant muscle LIM protein is associated with hypertrophic cardiomyopathy and exhibits altered binding properties in the system MLP - N-RAP - alpha-actinin}, issn = {0171-9335}, year = {2004}, language = {en} } @article{GehmlichGeierOsterzieletal.2004, author = {Gehmlich, Katja and Geier, C. and Osterziel, Karl Joseph and VanderVen, Peter F. M. and F{\"u}rst, Dieter Oswald}, title = {Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy}, issn = {0302-766X}, year = {2004}, abstract = {Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy. We show that MLP can form a ternary complex with two of its previously documented myofibrillar ligand proteins, N-RAP and alpha-actinin, which indicates the presence of distinct, non-overlapping binding sites. Our data also show that, in comparison to wild-type MLP, the capacity of the mutated MLP protein to bind both N-RAP and alpha-actinin is significantly decreased. In addition, this single point mutation prevents zinc coordination and proper folding of the second zinc-finger in the first LIM domain, which consequently renders the protein less stable and more susceptible to proteolysis. The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin. This assumption is supported by the previous observation that in the pathological situation accompanied by MLP down regulation, cardiomyocytes try to compensate for the decreased stability of MLP protein by increasing the expression of its ligand N-RAP, which might finally result in the development of myocyte disarray that is characteristic of this disease}, language = {en} } @article{PacholskyVakeelHimmeletal.2004, author = {Pacholsky, Dirk and Vakeel, Padmanabhan and Himmel, Mirko and Lowe, T. and Stradal, T. and Rottner, K. and F{\"u}rst, Dieter Oswald and vanderVen, Peter F. M.}, title = {Xin repeats define a novel actin-binding motif}, issn = {0021-9533}, year = {2004}, abstract = {Xin is a protein that is expressed during early developmental stages of cardiac and skeletal muscles. Immunolocalization studies indicated a peripheral localization in embryonic mouse heart, where Xin localizes with beta- catenin and N-cadherin. In adult tissues, Xin is found primarily in the intercalated discs of cardiomyocytes and the myotendinous junctions of skeletal muscle cells, both specialized attachment sites of the myofibrillar ends to the sarcolemma. A large part of the Xin protein consists of unique 16 amino acid repeats with unknown function. We have investigated the characteristics of the Xin repeats by transfection experiments and actin-binding assays and ascertained that, upon expression in cultured cells, these repeats bind to and stabilize the actin-based cytoskeleton. In vitro co- sedimentation assays with skeletal muscle actin indicated that they not only directly bind actin filaments, but also have the capability of arranging microfilaments into networks that sediment upon low-speed centrifugation. Very similar repeats were also found in Xin-repeat protein 2' (XIRP2), a novel protein that seems to be expressed mainly in striated muscles. Human XIRP2 contains 28 Xin repeats with properties identical to those of Xin. We conclude that the Xin repeats define a novel, repetitive actin-binding motif present in at least two different muscle proteins. These Xin- repeat proteins therefore constitute the first two members of a novel family of actin-binding proteins}, language = {en} } @article{HimmelVanderVenStoeckleinetal.2003, author = {Himmel, Mirko and VanderVen, Peter F. M. and St{\"o}cklein, Walter F. M. and F{\"u}rst, Dieter Oswald}, title = {The limits of promiscuity : isoform-specific dimerization of filamins}, year = {2003}, language = {en} } @article{ChakharovaWehnertUhletal.2000, author = {Chakharova, Christina and Wehnert, Manfred and Uhl, K. and Sekthivel, S. and Vorsberg, Hans-Peter and F{\"u}rst, Dieter Oswald}, title = {Genomic structure and fine mapping of the two human filamin gene paralogues FLNB and FLNC and comparative analysis of the filamin gene family}, year = {2000}, language = {en} }