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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:
Agata Pytyś, Rabia Ijaz, Anna Buszka, Jacek Miłek, Izabela Figiel, Patrycja Wardaszka, Matylda Roszkowska, Natalia Mierzwa, Adam Wojtas, Eli Kerstein, Remigiusz Serwa, Katarzyna Kalita, Rhonda Dzakpasu, Magdalena Dziembowska, Jakub Włodarczyk, Tomasz Wójtowicz (2025) Temporal and protein-specific S-palmitoylation supports synaptic and neural network plasticity.
Krzystyniak A., Gluchowska A., Pytyś A., Dudkowska M., Wójtowicz T., Targonska A., Janiszewska D., Sikora E., Mosieniak G. (2024) 2-Bromopalmitate treatment attenuates senescence phenotype in human adult cells - possible role of palmitoylation. Aging 23;16(16):11796-11808. DOI: 10.18632/aging.206080
Buszka, A., Pytyś, A., Colvin, D., Włodarczyk, J., & Wójtowicz, T. (2023). S-palmitoylation of synaptic proteins in neuronal plasticity in normal and pathological brains. Cells, 12(3), 387. doi: https://doi.org/10.3390/cells12030387
Ziółkowska, M., Borczyk, M., Cały, A., Tomaszewski, K. F., Nowacka, A., Nalberczak-Skóra, M., Śliwińska M. A., Łukasiewicz K., Skonieczna E., Wójtowicz T., Włodarczyk J., Bernaś T., Salamian A., & Radwanska, K. (2023). Phosphorylation of PSD-95 at serine 73 in dCA1 is required for extinction of contextual fear. Plos Biology, 21(5), e3002106. doi: https://doi.org/10.1371/journal.pbio.3002106
Organized events:
"Neurons in Action 2025" 28th May - 30st May 2025 symposium " The heterogeneity of protein lipid modifications in the brain " at the Nencki Institute.
Chairs: Tomasz Wójtowicz, Magdalena Czekalska
https://neuronsinaction.nencki.edu.pl/
"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".
Results presented during international conferences:
POSTER SFN Washington 2023.pdfProtein 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.pdfProtein 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.pdfProtein 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.pdfDynamic 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):
“Exploring S-Palmitoylation Dynamics in Synaptic Plasticity Using cLTP-Stimulated Synaptoneurosomes” | Rabia Ijaz, Agata Pytyś, Jacek Miłek, Magdalena Dziembowska, 8th International PhD Students Conference, Nencki Institute of Experimental Biology Polish Academy of Sciences, 8-9 Oct 2024
„ Protein palmitoylation in neuronal plasticity, learning, and memory” | T. Wójtowicz, Conference Palmitoylation in healthy and diseased brain, Nencki Institute of
Experimental Biology Polish Academy of Sciences, 3 Sep 2024
“Temporal and target-specific S-palmitoylation of proteins supports synapse and neural network plasticity” | T. Wójtowicz, International Centre for Translational Eye Research 12 Nov 2024
“Temporal and target-specific S-palmitoylation of proteins supports synapse and neural network plasticity” | T. Wójtowicz, Centre of New Technologies, University of Warsaw, 6 Dec 2024
"Neuroproteomics: Overview of Proteomics and its implementation in Neuroscience" | Domnic Colvin, Centre of New Technologies (CeNT) - University of Warsaw, 8th Mar. 2024
“The role of protein palmitoylation in functional aspects of synaptic and neural network plasticity” | T.Wójtowicz, Synaptic Plasticity Club, Nencki Institute, 14th Dec. 2023
"The role of lipid modifications of proteins in functional neuronal plasticity, learning and memory" | T.Wójtowicz, Centre of New Technologies (CeNT) - University of Warsaw, 3rd Dec. 2021
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