Uncovering the essential roles of human GCP 2 orthologs inCaenorhabditis elegans

Abstract

AbstractHuman glutamate carboxypeptidase 2 (GCP2) from the M28B metalloprotease group is an important target for therapy in neurological disorders and an established tumor marker. However, its physiological functions remain unclear. To better understand general roles, we used the model organismCaenorhabditis elegansgenetically manipulate its three existing orthologous genes and evaluate the impact on worm physiology. The results of gene knockout studies showed thatC. elegansGCP2 orthologs affect the pharyngeal physiology, reproduction, and structural integrity of the organism. Promoter-driven GFP expression revealed distinct localization for each of the three gene paralogs, withgcp-2.1being most abundant in muscles, intestine, and pharyngeal interneurons,gcp-2.2restricted to the phasmid neurons, andgcp-2.3located in the excretory cell. This study provides new insight into the unique phenotypic effects of GCP2 gene knockouts inC. elegans, and the specific tissue localizations. We believe that elucidation of particular roles in a non-mammalian organism can help to explain important questions linked to human GCP2 physiology and in extension to GCP2 involvement in pathophysiological processes.