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

作者：Rehberg Kati; Kliche Stefanie; Madencioglu Deniz A; Thiere Marlen; Mueller Bettina; Meineke Bernhard Manuel; Freund Christian; Budinger Eike; Stork Oliver^*

来源：Journal of Neuroscience, 2014, 34(15): 5342-5354.

DOI：10.1523/JNEUROSCI.2728-13.2014

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

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 Thr(788/789) of beta 1-integrin to stimulate the PKC- and CaMKII-dependent activation of beta 1-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 beta 1-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.

• 出版日期2014-4-9