| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The PAR-aPKC system plays crucial roles in establishing the apicobasal polarity of epithelial cells. On the other hand, the importance of extracellular matrix (ECM) components, especially laminin, in determining the orientation of the epithelial polarity axis has recently been established. However, molecular links between the PAR-aPKC system and ECM are still missing. In this work, we revealed that one component of the PAR-aPKC system, PAR-lb kinase, regulates extracellular laminin organization by controlling the localization and function of the laminin receptor complex, i.e. the utrophin-dystroglycan (DG) complex. PAR-lb exerts this function, at least in part, by directly phosphorylating Ser-814 of DG. Through this regulatory pathway, PAR-lb plays indispensable roles in ECM-directed apical pole orientation in epithelial cells. The present results reveal a novel inside-out pathway, .by which the intrinsic PAR-aPKC system regulates the extrinsic polarity cue essential for integrating the polarity axes of individual cells in epithelial tissues. Since PAR-lb knockdown induces DG hypoglycosylation, the present results also imply an unexpected link between cell polarity proteins and congenital muscular dystrophies caused by defects in known or putative glycosyltransferases.
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