Protein Targeting to Neuronal LDCVs

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Abstract

Proteins must be directed to different places within a cell, particularly in nerve cells (neurons), where long processes like the axon can extend far from the cell body. This protein 'traffic' is thought to be done by packaging proteins into distinct vesicles, which then are targeted to the correct destination. Virtually nothing is known about this process. Two principal types of vesicles are the large dense-core vesicles (LDCVs) containing neuropeptides or monoamines, and small clear vesicles (SCVs) that contain neurotransmitters like gultamate and gamma-amino butyric acid (GABA). Neurons and neuroendocrine cells both must correctly sort peptide precursors into LDCVs, away from the neurotransmitter-containing SCVs that release and reload their contents through very different mechansims. This project uses molecular and immunocytochemical approaches to identify polypeptide sequences that target VGF to LDCVs and to characterize the novel sorting mechanism or receptor molecule involved. Results will be important for defining the fundamental mechanisms that underly the sorting of proteins into distinct vesicle populations, ultimately transporting them to specific regions in highly polarized neurons, and to regions related to regulative or constitutive secretory pathways in these complex cells. Graduate training is included in this project.