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- Title
The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth.
- Authors
Rehberg, Kati; Kliche, Stefanie; Madencioglu, Deniz A.; Thiere, Marlen; Müller, Bettina; Meineke, Bernhard Manuel; Freund, Christian; Budinger, Eike; Stork, Oliver
- 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 ofβ1-integrin to stimulate the PKC- and CaMKII-dependent activation ofβ1-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 activatedβ1-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 3Aβ/β-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.
- Subjects
DEVELOPMENTAL neurobiology; NEURON development; PHOSPHORYLATION; HIPPOCAMPUS (Brain); SERINE/THREONINE kinases; TRANSGENIC mice
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 15, p5342
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2728-13.2014