Versatility by processing: proprotein convertases and their role in expanding neuropeptidergic diversity.

Neuropeptides are signaling molecules used by all Metazoan nervous systems to control physiology and behavior. They are produced by extensive processing from larger protein precursors. In mammals, examples are known where this processing can lead to distinct sets of neuropeptides in different tissues, due to differential expression of the proprotein convertases; a family of proteases responsible for cleavage of the protein precursors. However, apart from these few examples, little is known on how extensive differential processing is, and how proprotein convertases might be responsible for expanding signaling diversity in the nervous system. Via this project proposal, I am to address ignorance regarding this level of control, and provide detailed information on the prevalence and functional impact of differential processing. To unveil fundamental principles of differential neuropeptide processing, I intend to use peptidomics on the model organism Caenorhabditis elegans, an organism for which I can also map the differentially processed neuropeptides and their proprotein convertases precisely to the individual cells or tissues where these are produced. This information will guide functional studies, where I aim to unveil the physiological impact of differential neuropeptide processing. Overall, this work aims to provide insight into how differential processing can functionally diversify the neuropeptide arsenal, as generated from a fixed set of precursors.

Keywords:PROTEOMICS, NEUROPEPTIDES

Disciplines:Animal biochemistry, Animal cell and molecular biology, Invertebrate biology, Transcription and translation, Proteomics

Project type:Collaboration project