Huntingtons Disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of a trinucleotide repeat (CAG) in the gene encoding huntingtin (htt). This trinucleotide repeat is translated into an expanded polyglutamine stretch near the amino terminus of htt, affecting the interaction of htt with other proteins including an increase in binding to Huntingtin Associated Protein 1 (HAP1). In rodents and primates, HAP1 is mostly found in the brain where it is expressed in neurons. Although several functions have been proposed for HAP1, its role has not yet been clearly established. Here we report on the identification of a HAP1 C.elegans homolog called T27A3.1. T27A3.1 shows conservation with rat and human HAP1 as well as with Milton, a Drosophila HAP1 homolog. T27A3.1 is also part of a larger family of proteins including GABA interacting factor (GRIF) and O-Glnc transferase interacting protein. To determine the cellular expression of T27A3.1 (multiple isoforms; a-e), we generated several, transgenic worm lines expressing a fluorescent reporter protein (GFP and DsRed2) under the control of the promoter for T27A3.1. We have found that T27A3.1 is expressed in many cell types including a subset of chemosensory neurons in the head and tail. These include the amphid chemosensory neurons ASKL and R, ASIL and R, ADFL and ASEL; the phasmid neurons PHBL and R; and the CAN neurons which are required for worm survival. We are now generating specific antibodies to determine the cellular and subcellular localization of T27A3.1. We plan to determine the phenotypic effects of overexpressing and silencing T27A3.1 and have obtained an intragenic deletion of T27A3.1 (
tm1572) from Dr. Mitani (NBP-Japan).