Integrins are heterodimeric cell surface molecules that are able to recognize extracellular matrix, diffusible signals and other cells. They are critically involved in the proliferation, migration and differentiation of neurons. Integrins also play a key role in the modulation of synaptic plasticity and the associated changes in the synaptic cytoskeleton.
We have identified the serine/threonine kinase Ndr2 as a novel regulator for the intracellular trafficking of neuronal integrins and their activation at the cell surface. The kinase links the Hippo signalling pathway to neuronal differentiation and plasticity. We are also investigating how downstream of integrin receptors and cytoskeleton interact and contributes to the dendritic growth and branching in neurons.
These microscopic images show neuronal cells in culture, stained for the microtubule associated protein 2, MAP2 (red, on the left), and filled with green fluorescence protein (GFP, on the right).This labelling allows us to study to growth and differentiation of dendrites and synapses on different integrin substrates and their dependence on the expression of integrin receptors by these cells.
Waldt N, Seifert A, Demiray YE, Devroe E, Turk BE, Reichardt P, Mix C,Reinhold A, Freund C, Müller AJ, Schraven B, Stork O, Kliche S. Filamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells. Front Immunol. 2018 9:2852
Demiray YE, Rehberg K, Kliche S, Stork O. Ndr2 kinase controls neurite outgrowth and dendritic branching through alpha1 integrin expression. Front. Mol. Neurosci. 2018; 11:66.
Thiere M, Kliche S, Müller B, Teuber J, Nold I, Stork O. Integrin Activation Through the Hematopoietic Adapter Molecule ADAP Regulates Dendritic Development of Hippocampal Neurons. Front. Mol. Neurosci. 2016 Sep; 9:91.
Rehberg, K., Kliche, S., Madencioglu, D. A., Thiere, M., Muller, B., Meineke, B. M., Freund, C., Budinger, E., Stork, O. (2014). The serine/threonine kinase Ndr2 controls integrin trafficking and integrin-dependent neurite growth. The Journal of Neuroscience, 34(15), 5342–5354. doi:10.1523/JNEUROSCI.2728-13.2014
German Research Foundation. Research Grant STO488/4. Role of the serine/threonin kinase Ndr2 in integrin-mediated neural plasticity and learning.
PI: Prof. Dr. Oliver Stork
Collaboration partners: Prof. Dr. Alexander Dityatev (DZNE Magdeburg), Dr. Stefanie Kliche (OVGU Magdeburg)
Researchers: Dr. Deniz Ashan Madencioglu-Kul, M.Sc. Yunus Emre Demiray, Dr. Atsuhiro Tsuchija, M.Sc. Hussam Hayani (DZNE Magdeburg)