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Palmitoylation controls NMDA receptor function and steroid sensitivity
Ladislav Vyklický, PhD
Professor of Normal and Pathological Physiology
Institute of Physiology CAS
Third Faculty of Medicine
Charles University Prague
Czech Republic 🇨🇿
Biography: Ladislav Vyklický is the Head of the Laboratory of Cellular Neurophysiology at the Institute of Physiology CAS and a Professor of Normal and Pathological Physiology at the Third Faculty of Medicine, Charles University Prague. He obtained his M.D. degree from Charles University in Prague in 1981 and his Ph.D. in physiology and pathophysiology from the Institute of Physiology, Czechoslovak Academy of Sciences. He conducted postdoctoral research as a Fogarty Visiting Fellow and Fogarty Visiting Scientist in the Laboratory of Developmental Neurobiology, NIH, Bethesda, Maryland, USA (with Mark L. Mayer). Additionally, he held a Visiting Scientist position at the Max-Planck Institute for Cell Physiology in Heidelberg, Germany (with Professor Bert Sakmann). He was awarded the Prize of the Czechoslovak Academy of Sciences (1991) and the International Research Scholar Award from the Howard Hughes Medical Institute (1995–1999). In 2015–2020 he served as a Deputy Director of the Institute of Physiology CAS.
Prof. Vyklický's current research interests include the investigation of the functional and pharmacological properties of N-methyl-D-aspartate (NMDA) receptors. An emphasis is placed on understanding the molecular, cellular, and behavioral aspects relevant to human missense and nonsense variants, which are studied in various models, including recombinant receptors and genetically modified mouse models. His group is also involved in studies on the modulation of NMDA receptors by neurosteroids.
Selected Publications
Kysilov B, Kuchtiak V, Krausova BH, Balik A, Korinek M, Fili K, Dobrovolski M,Abramova V, Chodounska H, Kudova E, Bozikova P, Cerny J, Smejkalova T, Vyklicky L (2024) Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids. Cell Mol Life Sci 81. Doi: 10.1007/s00018-023-05062-6
Candelas Serra M, Kuchtiak V, Kubik-Zahorodna A, Kysilov B, Fili K, Hrcka Krausova B, Abramova V, Dobrovolski M, Harant K, Bozikova P, Cerny J, Prochazka J, Kasparek P, Sedlacek R, Balik A, Smejkalova T, Vyklicky L (2024) Characterization of mice carrying a neurodevelopmental disease- associated GluN2B(L825V) variant. J Neurosci., Doi:10.1523/JNEUROSCI.2291-23.2024
Abramova V et al. (2023) Effects of Pregnanolone Glutamate and Its Metabolites on GABAA and NMDA Receptors and Zebrafish Behavior. Acs Chemical Neuroscience 14:1870-1883. Doi: 10.1021/acschemneuro.3c00131
Kysilov B, Hrcka Krausova B, Vyklicky V, Smejkalova T, Korinek M, Horak M, Chodounska H, Kudova E, Cerny J, Vyklicky L (2022) Pregnane-based steroids are novel positive NMDA receptor modulators that may compensate for the effect of loss-of-function disease-associated GRIN mutations. Br J Pharmacol 179:3970-3990. Doi: 10.1111/bph.15841
Hubalkova P, Ladislav M, Vyklicky V, Smejkalova T, Hrcka Krausova B, Kysilov B, Krusek J, Naimová Z, Korinek M, Chodounska H, Kudova E, Cerny J, Vyklicky L (2021) Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity. The Journal of Neuroscience 41:2119-2134. Doi: 10.1523/JNEUROSCI.2654-20.2021
Smejkalova T, Korinek M, Krusek J, Hrcka Krausova B, Candelas Serra M, Hajdukovic D, Kudova E, Chodounska H, Vyklicky L (2021) Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms. Br J Pharmacol 178:3888- 3904. Doi: 10.1111/bph.15529
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