TableEdit

Li, SH, Li, H, Torre, ER and Li, XJ (2000) Expression of huntingtin-associated protein-1 in neuronal cells implicates a role in neuritic growth. Mol. Cell. Neurosci. 16:168-83

Huntingtin-associated protein-1 (HAP1) binds more tightly to mutant huntingtin, but its function and distribution in neurites are not clear. Using PC12 cells and cultured hippocampal neurons, we found that two HAP1 isoforms, HAP1-A and HAP1-B, have different subcellular localizations. While most HAP1-B is diffusely distributed within the cytoplasm, HAP1-A is enriched in the growth cones and neuritic puncta of developing neurons. In mature neurons and adult brain neurons, however, HAP1-A is concentrated in axon terminals and associated with synaptic vesicles. Transfection of HAP1-A in PC12 cells significantly promotes neurite extension, with HAP1-A distributed in the distal regions of the growing neurites. Cotransfection of mutant huntingtin with HAP1-A in PC12 cells results in the accumulation of HAP1-A on huntingtin aggregates and the inhibition of neurite promotion by HAP1-A. This study suggests that HAP1-A has a function in neuritic development and synaptic function and that mutant huntingtin may alter this function.

PubMed Online version:10.1006/mcne.2000.0858

Amino Acid Sequence; Animals; Gene Expression Regulation, Developmental; Hippocampus/cytology; Hippocampus/embryology; Mice; Microscopy, Electron; Molecular Sequence Data; Mutagenesis/physiology; Nerve Tissue Proteins/analysis; Nerve Tissue Proteins/genetics; Neurites/chemistry; Neurites/physiology; Neurites/ultrastructure; Neurons/chemistry; Neurons/ultrastructure; PC12 Cells; Presynaptic Terminals/chemistry; Presynaptic Terminals/ultrastructure; Rats; Subcellular Fractions/chemistry; Transfection