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First published online May 28, 2005
doi: 10.1242/10.1242/jcs.02398

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New insights into Fat cadherins

RIKEN Center for Developmental Biology, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan

View larger version (14K): [in a new window]   Fig. 1. Schematic representation of the cadherin superfamily. Fat cadherin is the largest cadherin, with 34 cadherin repeats. Blue ovals and green circles indicate cadherin repeats and laminin A-G motifs, respectively. Yellow boxes indicate EGF motifs. The red box in Flamingo indicates the flamingo box. Classical cadherin is believed to associate with the actin cytoskeleton through the ß-catenin and -catenin complex (pink oval). Desmosomal cadherins associate with intermediate filaments through plakoglobin/desmoplakin (light blue oval). The variously colored rectangles indicate the intracellular domains of the cadherins.

View larger version (24K): [in a new window]   Fig. 2. Members of the Fat and Dachsous cadherin subfamilies. Drosophila has two Fat cadherins (Fat and Fat-like) and one Dachsous cadherin. In vertebrates, four Fat cadherins (Fat-J, Fat1, Fat2 and Fat3) and two Dachsous cadherins (Dachsous 1 and Dachsous 2) have been reported. Fat-J is probably the counterpart of Drosophila Fat. Fat1 and Fat3 resemble each other in their overall sequences, and they show weak similarity to Drosophila Fat-like. The precise length of Dachsous 2 has not been determined. The rectangular boxes depict the intracellular domains of the various Fats. The regions between the last cadherin repeat and the first EGF motif or the laminin A-G motif (for Fat2) of Fat cadherins show weak similarities to the Flamingo box, which is conserved in Flamingo cadherins (Usui et al., 1999).

View larger version (7K): [in a new window]   Fig. 3. A phylogenic tree of Fat cadherins. Full-length sequences of these molecules are compared.

View larger version (11K): [in a new window]   Fig. 4. Potential signaling cascades in Fat-dependent regulation of planar cell polarity (PCP). Four-jointed and Dachsous regulate (probably negatively) Fat. How Four-jointed and Dachsous regulate Fat and how Fat regulates the PCP pathway have not been currently clarified.

View larger version (20K): [in a new window]   Fig. 5. Fat1 appears to be involved in cell-cell contacts and lamellipodial dynamics at the leading edge. Fat1 localizes to early cell-cell contact sites, lamellipodial edges and the basolateral portion of polarized epithelia (red). Fat1 regulates actin dynamics by binding to Ena/VASP proteins at these sites. Whether Fat1 cadherins undergo homophilic interactions remains unknown.