TY - JOUR A1 - VanderVen, Peter F. M. A1 - Ehler, Elisabeth A1 - Vakeel, Padmanabhan A1 - Eulitz, Stefan A1 - Schenk, Jörg A. A1 - Milting, Hendrik A1 - Micheel, Burkhard A1 - Fürst, Dieter Oswald T1 - Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/ VASP N2 - 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 Y1 - 2006 UR - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/12255 ER -