lipid modifications of proteins

THE ROLE OF LIPID MODIFICATIONS OF PROTEINS IN FUNCTIONAL NEURONAL PLASTICITY, LEARNING AND MEMORY 

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.

We use a multidisciplinary approach to study general mechanisms governing brain plasticity in the physiological and pathophysiological states. Currently, we implement biochemical tools allowing detection of protein modifications in the nervous tissue (i.e. acyl-biotinyl exchange in brain homogenates and synaptoneurosomes) and mass spectrometry. To study functional aspects of neuronal networks, we combine pharmacology and single-cell patch-clamp technique or field potentials recording in primary hippocampal neurons and acute brain slices. Alternatively, we use Multi-Electrode-Arrays for long-term recordings of neuronal network activity. We also use immunofluorescence as well as live Ca2+ imaging to study Ca2+ dynamics in neurons and astrocytes. Recently we have introduced slice cultures where genes of interest are manipulated with viral vectors. 

POPULARIZATION OF THE RESULTS OF THE PROJECT:

Results published in the frame of the project 2019/34/E/NZ4/00387: 

Organized events:

"Protein palmitoylation in healthy and diseased brain" STER NAWA Advanced Lecture Series, 2nd-3rd September 2024 Nencki Institute, Warsaw, Poland 

Organizers: Tomasz Wójtowicz, Jakub Włodarczyk, Agata Pytyś

Chairs: Tomasz Wójtowicz, Jakub Włodarczyk

https://palmitoylation.nencki.edu.pl/


"Neurons in Action 2023"  31st May - 2nd June 2023 symposium "Mechanisms of brain disorders" at the Nencki Institute.
Chairs: Tomasz Wójtowicz, Jakub Włodarczyk


Rebeca Maria Mejias-Estevez (University of Seville, Spain) "Protein palmitoilation in dopaminergic alterations".

https://neuronsinaction.nencki.edu.pl/ 

Results presented during international conferences: 

POSTER SFN Washington 2023.pdf

Protein S-palmitoylation in hippocampal synaptic plasticity 

Tomasz Wójtowicz, Agata Pytyś, Anna Buszka, Matylda Roszkowska, Eli Kerstein, Rhonda Dzakpasu, Kasia Kalita-Bykowska, Jakub Włodarczyk

Neuroscience 2023 Congress

Washington, USA

11-15th Nov. 2023

Poster #: PSTR524.01/D42

P0826_Pytys_A0.pdf

Protein S-palmitoylation in synaptic plasticity 

Agata Pytyś, Anna Buszka, Izabela Figiel, Jakub Włodarczyk, Tomasz Wójtowicz 

36th Congress of European College of Neuropsychopharmacology

Barcelona, Spain

7-10th Oct. 2023


7 th PhD Students Conference

Nencki Insitute, Warsaw, Poland

19-20th Oct. 2023

POSTER PTBUN 2023.pdf

Protein S-palmitoylation in hippocampal synaptic plasticity

Tomasz Wójtowicz, Agata Pytyś, Anna Buszka, Matylda Roszkowska, Eli Kerstein, Rhonda Dzakpasu, Kasia Kalita-Bykowska, Jakub Włodarczyk

16th International Congress of the Polish Neuroscience Society  (PTBUN)

Toruń, Poland

20-23rd Sept. 2023 

Poster Neuronus.pdf

Dynamic S-palmitoylation of synaptic proteins

Agata Pytyś, Domnic Colvin, Rabia Ijaz, Jakub Włodarczyk, Tomasz Wójtowicz 

Neuronus 2024 Neuroscience Forum

Kraków, Poland

25-27th Apr. 2024

Presentation of the results (seminars):