Appropriate regulation of osteoclast-mediated bone resorption is essential for maintenance of healthy bone. Understanding the molecular regulation of osteoclasts may lead to new therapeutic approaches to common serious bone diseases like osteoporosis. Osteoclasts resorb bone by generating an acidic compartment on the bone surface. A key component of the osteoclast acid transport mechanism is a chloride channel which is expressed in the osteoclast-ruffled border. The applicant's long-term goals have been to identify the molecular basis of the ruffled border chloride channel and to understand how this channel may regulate acid transport and bone resorption.
The Specific Aims of the present proposal are to: (1) complete molecular cloning of the sequences encoding the ruffled membrane chloride channel; (2) biochemically characterize the channel complex; (3) explore the relationship between the chloride channel and the non-receptor tyrosine kinases, src, and; (4) define the mechanism by which the presence of bone regulates expression of the chloride channel.
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| Shanks, Ryan A; Larocca, M Cecilia; Berryman, Mark et al. (2002) AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member. J Biol Chem 277:40973-80 |
| Tulk, B M; Schlesinger, P H; Kapadia, S A et al. (2000) CLIC-1 functions as a chloride channel when expressed and purified from bacteria. J Biol Chem 275:26986-93 |
| Edwards, J C; Kapadia, S (2000) Regulation of the bovine kidney microsomal chloride channel p64 by p59fyn, a Src family tyrosine kinase. J Biol Chem 275:31826-32 |
