Analysis of Wnt signaling pathway mediated frizzled protein family

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Frizzled proteins play a role as a Wnt receptor and involved in the regulation of gene expression as well as planar cell polarity. Since carboxyl temini of many frizzled family members contain PDZ binding motifs, we isolated several candidate molecules that potentially interact with frizzled.One of these interacting proteins, fzip-1 , contains two coiled-coil motif and one PDZ domain. This molecule was named as Golgi-associated PDZ and coiled-coil motif containing protein (GOPC), as it was localized at the Golgi apparatus. A series of molecular studies indicates GOPC has a role in transport of frizzled form the Golgi apparatus to plasma membrane. Furthermore, Male GOPC knockout mouse was infertile due to abnormal acrosome formation. Electronmicrosopic analysis revealed that vesicle transport from the Golgi apparatus to acrosome was severely impaired. Thus it appears GOPC functions the vesicle transport to acrosome in addition to plasma membrane. We also found that the second interacting molecule; fzip-2, is involved in G protein dependent -JNK activation, whereas the third molecule, fzip-3, is suggested to function in cell division. We are currently investigating the molecular analysis of these molecules as well as their biological significance by gene targeting.