Regulation of intracellular HAP1 trafficking.

A number of proteins are known to interact with huntingtin (htt), the Huntington's disease (HD) protein. Understanding the function of these htt-associated proteins could help elucidate the pathogenesis of HD and the role that htt plays in the disease process. The present review focuses on one such protein, huntingtin-associated protein 1 (HAP1), which has proved to be involved in intracellular trafficking. Unlike huntingtin, which is expressed ubiquitously throughout the brain and body, HAP1 is enriched in neurons, suggesting that its dysfunction could contribute to the selective neuropathology in HD. HAP1 binds microtubule-dependent transporters that engage anterograde or retrograde transport and also associates with a variety of organelles and membrane receptors. This raises the interesting issue of how the HAP1 trafficking function is regulated. We discuss recent evidence for the involvement of HAP1 in intracellular trafficking as well as potential mechanisms that may regulate its trafficking. (c) 2007 Wiley-Liss, Inc.