Dishevelled

Dishevelled is one of the multi-module proteins working in the Wnt pathway. The DIX domain in Axin is similar to a domain in Dishevelled, and may promote interacions between these two domains (Hsu 1999). The protein has been found at multiple locations in cells, including the nucleus (Itoh, 2005)

While the mechanism of action of Dsh is not known, it interacts with a number of other molecules, including Casein Kinase 1 (CK1e); Peters 1999, Sakanaka, 1999) Casein Kinase 2 (CK2; Willert 1997 Song, 2003) and GBP/Frat1 (Li L1999, Salic, 2000; Farr 2000). CK1 appears to be important for Wnt signaling, both in Xenopus and in C. elegans ( Peters 1999). It should be noted that CK1 and CK2 are unrelated kinases. A third kinase interacting with Dsh is Par-1 (Sun et al, 2001). This kinase acts as a positive regaulator of Wnt signaling in Drosophila and in other systems; and can phosphorylate Dsh directly. Ossipova et al. (2005) have suggested that PAR-1A and PAR-1BX are essential for canonical signaling to beta-catenin. Dsh also Regules Lethal giant larvae and cell polarity (Dollar, 2005). The KLHL12-Cullin-3 ubiquitin ligase has been reported to target Dishevelled for degradation (Angers, 2006).

A mutagenesis screen of Dsh in Drosophila (Penton, 2002), has revealed several new alleles and domains in the protein. A diagram of the position of the mutations can be downloaded (PDF file)

A direct interaction between Dsh, GBP/Frat1 and Zw3/GSK may be the keystep in the inactivation of Zw3/GSK (Li L1999).

gene

chromosome location

 Phenotype

 Human DVL1  1p36  
 Human DVL2  17q21  
 Human DVL3  3q27  
Human Dvl1L1 22q
 Mouse Dvl1  4 Social interaction and sensorimotor gating abnormalities (Lijam, 1997)

Open neural tube as a double mutant with Dvl2 mutant (Hamblet, 2002)

convergent extension phenotype (with Dvl2 mutant) Wang et al, 2006

 Mouse Dvl2  11 cardiovascular outflow tract defect (Hamblet, 2002). Similar to Pitx2 phenotype (Kioussi, 2002). Open neural tube as a double mutant with Dvl1 mutant.

convergent extension phenotype (with Dvl1 mutant) Wang et al, 2006

 Mouse Dvl3 16 cardiac outflow tract (Etheridge 2008)
 Drosophila Dsh 10B Segment polarity, planar polarity
C elegans mig-5
Q cell migration

 

Dishevelled structure