title: DIXDC1 isoform, l-DIXDC1, is a novel filamentous actin-binding protein.
abstract: Ccd1, a DIX domain containing Zebrafish protein involved in neural patterning, is a positive regulator of the Wnt signaling pathway. DIXDC1, the human homolog of Ccd1, has two predominant isoforms. The short form (s-DIXDC1) has a similar amino acid sequence compared with Ccd1, while the long form (l-DIXDC1) contains an extra N-terminal sequence containing a calponin-homology (CH) domain, suggesting additional interaction with actin that we have performed detailed analysis in this report. We show that mRNA expression of both DIXDC1 isoforms can be detected in various adult tissues by Northern blot analysis and is most abundant in cardiac and skeletal muscles. Both endogenous and ectopically expressed l-DIXDC1, but not s-DIXDC1, in cultured mammalian cells is localized to actin stress fibers at the filament ends in focal adhesion plaques. More importantly, l-DIXDC1 can directly bind to filamentous actin both in vitro and in vivo and the binding is mediated via a novel actin-binding domain (ABD) from amino acid 127 to 300. Thus, our data provide the first evidence that l-DIXDC1 may act as a novel branching component in the Wnt signaling pathway targeting both beta-catenin-TCF complex for gene expression and cytoskeleton for regulating dynamics of actin filaments.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic/Mayo Medical School, Rochester, MN 55905, USA.
authors.forename: Xianshu
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Zhaozhu
authors.initials: Z
authors.lastname: Zeng
authors.forename: Guangjin
authors.initials: G
authors.lastname: Zhou
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chien
authors.forename: Chiping
authors.initials: C
authors.lastname: Qian
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
authors.forename: Viji
authors.initials: V
authors.lastname: Shridhar
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Wanguo
authors.initials: W
authors.lastname: Liu
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014018:Tissue Distribution
chemical_list: D003598:Cytoskeletal Proteins; C513335:DIXDC1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D020033:Protein Isoforms