TY - JOUR
T1 - DIXDC1 isoform, l-DIXDC1, is a novel filamentous actin-binding protein
AU - Wang, Xianshu
AU - Zheng, Li
AU - Zeng, Zhaozhu
AU - Zhou, Guangjin
AU - Chien, Jeremy
AU - Qian, Chiping
AU - Vasmatzis, George
AU - Shridhar, Viji
AU - Chen, Lin
AU - Liu, Wanguo
PY - 2006/8/18
Y1 - 2006/8/18
N2 - 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 β-catenin-TCF complex for gene expression and cytoskeleton for regulating dynamics of actin filaments.
AB - 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 β-catenin-TCF complex for gene expression and cytoskeleton for regulating dynamics of actin filaments.
KW - Actin-binding protein
KW - DIX domain
KW - DIXDC1
KW - Dvl
KW - Wnt signaling
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U2 - 10.1016/j.bbrc.2006.06.050
DO - 10.1016/j.bbrc.2006.06.050
M3 - Article
C2 - 16814745
AN - SCOPUS:33745746521
VL - 347
SP - 22
EP - 30
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -