MIM and Cortactin Antagonism Regulates Ciliogenesis and Hedgehog Signaling

被引:115
作者
Bershteyn, Marina [1 ,2 ]
Atwood, Scott X. [1 ]
Woo, Wei-Meng [1 ]
Li, Mischa [1 ]
Oro, Anthony E. [1 ]
机构
[1] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Canc Biol Grad Program, Stanford, CA 94305 USA
关键词
SONIC-HEDGEHOG; HAIR FOLLICLE; ACTIN POLYMERIZATION; RESPONSIVE GENE; IN-VITRO; CILIA; METASTASIS; INHIBITION; DYNAMICS; NETWORK;
D O I
10.1016/j.devcel.2010.07.009
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The primary cilium is critical for transducing Sonic hedgehog (Shh) signaling, but the mechanisms of its transient assembly are poorly understood. Previously we showed that the actin regulatory protein Missing-in-Metastasis (MIM) regulates Shh signaling, but the nature of MIM's role was unknown. Here we show that MIM is required at the basal body of mesenchymal cells for cilia maintenance, Shh responsiveness, and de novo hair follicle formation. MIM knockdown results in increased Src kinase activity and subsequent hyperphosphorylation of the actin regulator Cortactin. Importantly, inhibition of Src or depletion of Cortactin compensates for the cilia defect in MIM knockdown cells, whereas overexpression of Src or phospho-mimetic Cortactin is sufficient to inhibit ciliogenesis. Our results suggest that MIM promotes ciliogenesis by antagonizing Src-dependent phosphorylation of Cortactin and describe a mechanism linking regulation of the actin cytoskeleton with ciliogenesis and Shh signaling during tissue regeneration.
引用
收藏
页码:270 / 283
页数:14
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