PT  - JOURNAL ARTICLE
AU  - Kati Rehberg
AU  - Stefanie Kliche
AU  - Deniz A. Madencioglu
AU  - Marlen Thiere
AU  - Bettina Müller
AU  - Bernhard Manuel Meineke
AU  - Christian Freund
AU  - Eike Budinger
AU  - Oliver Stork
TI  - The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth
AID  - 10.1523/JNEUROSCI.2728-13.2014
DP  - 2014 Apr 09
TA  - The Journal of Neuroscience
PG  - 5342--5354
VI  - 34
IP  - 15
4099  - http://www.jneurosci.org/content/34/15/5342.short
4100  - http://www.jneurosci.org/content/34/15/5342.full
SO  - J. Neurosci.2014 Apr 09; 34
AB  - 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.