Expression of huntingtin-associated protein-1 in neuronal cells implicates a role in neuritic growth.
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.
Department of Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D016501:Neurites / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure*; D016716:PC12 Cells; D017729:Presynaptic Terminals / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D013347:Subcellular Fractions / Q000737:chemistry; D014162:Transfection
C490758:Hap1 protein, mouse; C490757:Hap1 protein, rat; D009419:Nerve Tissue Proteins