RT Journal Article
SR Electronic
T1 The Serine/Threonine Kinase Ndr2 Controls Integrin Trafficking and Integrin-Dependent Neurite Growth
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5342
OP 5354
DO 10.1523/JNEUROSCI.2728-13.2014
VO 34
IS 15
A1 Kati Rehberg
A1 Stefanie Kliche
A1 Deniz A. Madencioglu
A1 Marlen Thiere
A1 Bettina Müller
A1 Bernhard Manuel Meineke
A1 Christian Freund
A1 Eike Budinger
A1 Oliver Stork
YR 2014
UL http://www.jneurosci.org/content/34/15/5342.abstract
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.