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The Caenorhabditis elegans homologue of huntingtin interacting protein 1 has multiple roles in development Parker, Jodey Alexander

Abstract

Endocytosis is an essential process in all eukaryotes and is involved in biological processes such as nutrient uptake and neurotransmitter recycling. Mammalian cell culture and yeast genetic studies have implicated the HIP1/SLA2 family of genes in linking the actin cytoskeleton to endocytosis. The contribution of the cytoskeleton to endocytic events is not well understood. Human HIP1 is of medical importance as it has been shown to interact with huntingtin, and may be important to the etiology of Huntington disease. Analysis of this family of genes in a metazoan animal system, such as C. elegans or Drosophila is an area that has been largely unexplored. As endocytosis is a mechanism by which cells interact with their environments, the use of an animal system may be particularly informative as it may illustrate differences between unicellular and multicellular systems. Through a combination of gene disruption and molecular characterization techniques, I have studied the function of CeHIP1, the C elegans member of the HIP1/SLA2 gene family. CeHIP1 displays postembryonic, tissue-specific expression, and has several functions in the adult animal. CeHIP1 has a role in maintaining proper morphology and function of the pharynx, the nematode feeding structure. CeHIP1 is required for promoting fertilization; gene silencing results in reduced fecundity. The locus is dose sensitive. CeHIP1 is haploinsufficient, and overexpression results in reduced viability and death of the animals. C. elegans is an excellent model to interpret the function of the human homolog HIP1. Both CeHIP1 and HIP1 show restricted expression and display dose sensitive toxic effects, inferring a shared mode of action. This thesis describes the establishment of a simple animal model that may be used to delineate pathways common to both genes. These findings may reflect the situation in humans, and perhaps point out avenues of potential treatment for Huntington disease.

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