lipid modifications of proteins

Research funded by the National Science Centre - grant no. 2019/34/E/NZ4/00387

Amount of funding awarded: 3 564 000, 00 PLN

keywords: neuronal plasticity, learning and memory, dopamine, hippocampus, electrophysiology, palmitoylation, molecular biology, imaging

The hallmark of the mammalian brain is the ability of processing and store information in synapses and highly organized neuronal networks. The brain can adapt and change in response to various events under physiological conditions (i.e. learning and memory formation) and pathological conditions (i.e. epilepsy, stroke). Understanding the fundamental mechanisms governing the plasticity of synaptic connections and neuronal network code lies in the center of contemporary neuroscience, neuropharmacology, and medicine. The identification of posttranslational modifications (PTMs) opened a new dimension of how we understand protein structure and cellular function. In the last decade, reversible lipid modification of proteins called S-palmitoylation (S-PALM) has been shown to dynamically regulate the localization of several neuronal synaptic and non-synaptic proteins in vitro. However, the time-course and the functional consequences of S-PALM in neurons, its role in neural plasticity and learning remains unknown. Processes like a reward, motor function, and cognition are modulated by the neurotransmitter dopamine (DA). Novelty-driven DA release to the hippocampus is indispensable for the conversion of short-term memories to long-term ones (memory consolidation). Interestingly, in vitro, recombinant DA receptors and transporters are subject to S-PALM.

Our current project focuses on the description of the time-course of S-PALM following various patterns of neuronal activity and the role of protein S-PALM in dopamine- and hippocampus-dependent learning.