Dr Vladimir Sytnyk
- 2002-4 Postdoctoral Fellow, Institute for Biosynthesis of Neuronal Structures, Centre for Molecular Neurobiology, Hamburg, Germany.
- 2004-9 Group Leader, Institute for Biosynthesis of Neuronal Structures, Centre for Molecular Neurobiology, Hamburg, Germany.
The major focus of my research is on the mechanisms via which adhesion molecules of the immunoglobulin superfamily regulate the development and functioning of the brain cells – neurons.
Adhesion molecules are present at the cell surface of neurons where they function as “short-range detectors” of the environment surrounding neurons. In developing neurons, these molecules either facilitate or block neuronal growth and differentiation depending on whether the environment is permissive or inhibitory. In mature neurons, cell adhesion molecules stabilise contacts between neurons and neurons and other cells. Cell adhesion molecules also accumulate in synapses – specialised contacts between neurons that allow neurons to transmit information to each other. Importantly, most models of learning and memory invoke modification of synaptic strength as the underlying mechanism for information storage and processing in the brain.
Previous work of the group members published in The Journal of Cell Biology and Neuron showed that two adhesion molecules, NCAM and CHL1, accumulate in synapses and regulate synapse assembly and functioning. In recent research conducted in BABS, we have identified several new adhesion molecules that accumulate at synapses. Using mice as an animal model and cultured neurons as a cellular model, the group is now investigating the functions that these cell adhesion molecules play in synapses and how mutations or abnormal expression of these molecules can inflict or contribute to the brain disorders, including schizophrenia, Alzheimer’s disease, X-linked disorders and Down Syndrome.
An important direction of my work is the investigation of how the posttranslational modifications of cell adhesion molecules regulate their functions. Acylation, glycosilation and phosphorylation of the cell adhesion molecules and their involvement in neuritogenesis and synapse formation are currently being investigated.
Our hope is that this research will lead to better understanding of the aetiology of the brain disorders and will ultimately provide tools to treat these disorders.
- Cell adhesion molecules in regulation of neuronal differentiation, synapse formation and function
- Post-translational modifications of adhesion molecules in healthy and diseased brains
ACTIVE RESEARCH PROJECTS
Tian, N., Leshchyns'ka, I., Welch, J., Diakowski, W., Yang, H., Schachner, M. & Sytnyk, V. (2012)
Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis.
The Journal of Biological Chemistry. 287(53): 4447-44463.
Poplawski, G.H.D., Transziska, A.K., Leshchyns'ka, I., Meier, I.D., Streichert, T., Sytnyk, V., & Schachner, M. (2012)
L1CAM increases MAP2 expression via the MAPK pathway to promote neurite outgrowth.
Molecular and Cellular Neuroscience , 50, pp. 169 - 178.
Yang, H., Galea, A.M., Sytnyk, V., & Crossley, M. (2012)
Controlling the size of lipid droplets: Lipid and protein factors.
Current Opinion in Cell Biology. 24(4): 509-516.
Leshchyns'ka, I., Tanaka, M., Schachner, M. & Sytnyk, V. (2011)
Immobilized pool of NCAM180 in the postsynaptic membrane is homeostatically replenished by the flux of NCAM180 from extrasynaptic regions.
The Journal of Biological Chemistry. 286(26): 23397-23406.
Puchkov, D., Leshchyns’ka, I., Nikonenko, A., Schachner, M. & Sytnyk, V. (2011)
NCAM/spectrin complex disassembly results in PSD perforation and postsynaptic endocytic zone formation.
Cerebral Cortex. 21: 2217-2232.
Chernyshova, Y., Leshchyns'ka, I., Hsu, Shu-Chan, Schachner, M. & Sytnyk, V. (2011)
The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones.
The Journal of Neuroscience. 31: 3522-3535.
Westphal, D., Sytnyk, V., Schachner, M. & Leshchyns'ka I. (2010)
Clustering of the neural cell adhesion molecule (NCAM) at the neuronal cell surface induces caspase-8- and -3-dependent changes of the spectrin meshwork required for NCAM-mediated neurite outgrowth.
The Journal of Biological Chemistry. 285: 42046-42057.
Andreyeva, A., Leshchyns'ka, I., Knepper, M., Betzel, C., Redecke, L., Sytnyk, V. & Schachner, M. (2010)
CHL1 is a selective organizer of the presynaptic machinery chaperoning the SNARE complex.
PLoS One. 5(8): e12018.
Devanathan, V., Jakovcevski, I., Santuccione, A., Li, S., Lee, H.J., Peles, E., Leshchyns'ka, I., Sytnyk, V. & Schachner, M. (2010)
Cellular form of prion protein inhibits Reelin-mediated shedding of Caspr from the neuronal cell surface to potentiate Caspr-mediated inhibition of neurite outgrowth.
The Journal of Neuroscience. 30: 9292-9305.
Schachner, M., Leshchyns’ka, I. & Sytnyk, V. (2009)
The neural cell adhesion molecule NCAM and its postsynaptic functions.
In Encyclopedia of Neuroscience. Elsevier/Great Britain, Oxford.
Bodrikov, V., Sytnyk, V., Leshchyns'ka, I., den Hertog, J. & Schachner, M. (2008)
NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its catalytic activity and enhance neurite outgrowth.
The Journal of Cell Biology. 182(6): 1185-1200.