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Articles, Cellular/Molecular

The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth

Kati Rehberg, Stefanie Kliche, Deniz A. Madencioglu, Marlen Thiere, Bettina Müller, Bernhard Manuel Meineke, Christian Freund, Eike Budinger and Oliver Stork
Journal of Neuroscience 9 April 2014, 34 (15) 5342-5354; https://doi.org/10.1523/JNEUROSCI.2728-13.2014
Kati Rehberg
1Department of Genetics and Molecular Neurobiology, Institute of Biology, and
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Stefanie Kliche
2Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany,
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Deniz A. Madencioglu
1Department of Genetics and Molecular Neurobiology, Institute of Biology, and
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Marlen Thiere
1Department of Genetics and Molecular Neurobiology, Institute of Biology, and
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Bettina Müller
1Department of Genetics and Molecular Neurobiology, Institute of Biology, and
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Bernhard Manuel Meineke
3Department of Biochemistry, Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany,
4Protein Engineering Group, Leibniz-Institute for Molecular Pharmacology, 13125 Berlin, Germany,
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Christian Freund
3Department of Biochemistry, Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany,
4Protein Engineering Group, Leibniz-Institute for Molecular Pharmacology, 13125 Berlin, Germany,
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Eike Budinger
5Department of Auditory Learning and Speech, Leibniz-Institute for Neurobiology, 39118 Magdeburg, Germany, and
6Center for Behavioral Brain Sciences, 39106 Magdeburg, Germany
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Oliver Stork
1Department of Genetics and Molecular Neurobiology, Institute of Biology, and
6Center for Behavioral Brain Sciences, 39106 Magdeburg, Germany
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Abstract

Integrins have been implicated in various processes of nervous system development, including proliferation, migration, and differentiation of neuronal cells. In this study, we show that the serine/threonine kinase Ndr2 controls integrin-dependent dendritic and axonal growth in mouse hippocampal neurons. We further demonstrate that Ndr2 is able to induce phosphorylation at the activity- and trafficking-relevant site Thr788/789 of β1-integrin to stimulate the PKC- and CaMKII-dependent activation of β1-integrins, as well as their exocytosis. Accordingly, Ndr2 associates with integrin-positive early and recycling endosomes in primary hippocampal neurons and the surface expression of activated β1-integrins is reduced on dendrites of Ndr2-deficient neurons. The role of Ndr2 in dendritic differentiation is also evident in vivo, because Ndr2-null mutant mice show arbor-specific alterations of dendritic complexity in the hippocampus. This indicates a role of Ndr2 in the fine regulation of dendritic growth; in fact, treatment of primary neurons with Semaphorin 3A rescues Ndr2 knock-down-induced dendritic growth deficits but fails to enhance growth beyond control level. Correspondingly, Ndr2-null mutant mice show a Semaphorin 3A−/−-like phenotype of premature dendritic branching in the hippocampus. The results of this study show that Ndr2-mediated integrin trafficking and activation are crucial for neurite growth and guidance signals during neuronal development.

  • dendritic and axonal growth
  • dendritic branching
  • integrin activation
  • integrin trafficking
  • mouse
  • serine/threonine kinase Ndr2
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The Journal of Neuroscience: 34 (15)
Journal of Neuroscience
Vol. 34, Issue 15
9 Apr 2014
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The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth
Kati Rehberg, Stefanie Kliche, Deniz A. Madencioglu, Marlen Thiere, Bettina Müller, Bernhard Manuel Meineke, Christian Freund, Eike Budinger, Oliver Stork
Journal of Neuroscience 9 April 2014, 34 (15) 5342-5354; DOI: 10.1523/JNEUROSCI.2728-13.2014

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The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth
Kati Rehberg, Stefanie Kliche, Deniz A. Madencioglu, Marlen Thiere, Bettina Müller, Bernhard Manuel Meineke, Christian Freund, Eike Budinger, Oliver Stork
Journal of Neuroscience 9 April 2014, 34 (15) 5342-5354; DOI: 10.1523/JNEUROSCI.2728-13.2014
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Keywords

  • dendritic and axonal growth
  • dendritic branching
  • integrin activation
  • integrin trafficking
  • mouse
  • serine/threonine kinase Ndr2

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