MOLECULAR/CELLULAR ACTION OF CRANIN IN NEURAL CELLS

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the extracullular matrix protein laminin is extremely potent in stimulating and guiding the growth of axons. Moreover, it is expressed in the developing and regenerating brain, in parallel with active axonal outgrowth. The effects of laminin may be clinically important in promoting recovery following brain insults, because exogenous grafts containing laminin coated surfacts can permit regeneration of axons to occur within the central nervous system of adult mammals. Neural cells interact with laminin via cell surface molecules. The first step in understanding how laminin's neurite printing effects can be regulated or facilitated is to learn the identities and roles of the laminin-binding proteins found on neural cell surfaces. This proposal tests the hypothesis that a newly discovered laminin-binding protein, cranin, is critical in mediating some of laminin's actions on neural cells. Antibodies will bs raised against cranin that block its binding to laminin. Neural cells will be exposed to these antibodies to test whether their behavioral responses to laminin will be altered. These or other anti-cranin antibodies will also be alloyed to describe the pattern of cranin's expression in developing and regenerating brain, and to examine possible structural modifications of cranin that occur as a function of developmental stags, types of tissue, or under different physiologic conditions. the binding of cranin to laminin will also be examined, for example to test whether cranin binds to a domain of laminin with known neurite promoting activity or other#r bioactivities. Thus. a broad body of both direct and correlative evidence will be adduced to suggest the nature of cranin's roles in neural cells. The molecular cloning of cranin will be completed. This will allow its amino acid sequence and other detailed structural features to be deduce. Furthermore, cranin deficient cells will be transfected with cranin cDNA and assayed for new responsiveness to laminin. This will provides a conclusive test of cranin's proposed role as a laminin 'receptor'. Cranin may be critical in regulating the ability of axons to extend or regenerate under certain conditions, hence it is important to understand cranin's structure and function. Information gained via cloning may lead to news means of controlling the expression of cranin in brain, and thus promote optimal axonal growth both in the fetus and in the adult human following insults.