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Papers In Press, published online ahead of print December 8, 2005
Human Genetics, Emory University, Atlanta, GA 30322
Corresponding Author: xiaoli{at}genetics.emory.edu
Huntingtin associated protein-1 (HAP1) was initially identified as an interacting partner of huntingtin, the Huntington disease (HD) protein. Unlike huntingtin, which is ubiquitously expressed throughout the brain and body, HAP1 is enriched in neurons, suggesting that its dysfunction could contribute to HD neuropathology. Growing evidence has demonstrated that HAP1 and huntingtin are anterogradely transported in axons and that the abnormal interaction between mutant huntingtin and HAP1 may impair axonal transport. However, the role of HAP1 in anterograde transport remains unclear. Here we report that HAP1 interacts with kinesin light chain (KLC), a subunit of the kinesin motor complex that drives anterograde transport along microtubules. The interaction of HAP1 with KLC is demonstrated via a yeast-two hybrid assay, glutathione S-transferase pull down, and coimmunoprecipitation. Furthermore, HAP1 is colocalized with kinesin in growth cones of neuronal cells. We also demonstrate that knocking down HAP1 via siRNA suppresses neurite outgrowth of PC12 cells. In addition, analysis of live neuronal cells with fluorescence microscopy and Fluorescence Recovery After Photobleaching (FRAP) demonstrates that suppressing HAP1's expression or deleting the HAP1 gene inhibits the kinesin-dependent transport of amyloid precursor protein (APP) vesicles. These studies provide a molecular basis for the participation of HAP1 in anterograde transport in neuronal cells.
J. Biol. Chem, 10.1074/jbc.M509806200
Submitted on September 7, 2005
Revised on December 7, 2005
Accepted on December 8, 2005
Interaction of huntingtin-associated protein-1 with kinesin light chain: Implications in intracellular trafficking in neurons
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