BIOLOGICAL ROLE OF PROTOCADHERINS IN CNS

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The central nervous system requires complicated cell-cell interactions for its structural formation and myriad functions, and cell adhesion seems to play an important role many of these events. Understanding cell adhesion molecules, mediate Ca2+ dependent, selective cell-cell adhesion in many biological processes. However, only one type of cadherin form the central nervous system has been studied extensively. Using polymerase chain reaction, we have recently isolated many cDNAs that correspond to new cadherins and to cadherin-related proteins, termed protocadherins, from rat and human brain cDNA preparations. In this proposed study we will focus on protocadherins, because many of these proteins are expressed mainly in brain, because their expression is regulated developmentally, and because they have the properties of adhesion proteins. The long-term goal of the proposed study is elucidation of the biological role of protocadherins in the central nervous system. We will study the basic properties of these newly isolated protocadherins in order to clarify their role, especially the role in nervous tissue formation and maintenance. We will (1) determine the entire amino acid sequences of two protocadherins; (2) express the protocadherins form cloned cDNAs in various cells and examine their basic biochemical an biological properties; (3) examine the tissue and cellular localization of these protocadherins, and the regulation of their expression; (4) examine the effect of ectopic expression of protocadherin pc 2 and its altered form on development of neural retina; and (5) characterize the gene of protocadherin pc2. The results will provide basic information i valuable for information valuable for understanding the biological role of theses proteins under physiological and pathological conditions, and may hale implications for understanding some neural disease, such as developmental disorders an neural degeneration.