PT  - JOURNAL ARTICLE
AU  - Shih-Hsiu J. Wang
AU  - Ivana Celic
AU  - Se-Young Choi
AU  - Martin Riccomagno
AU  - Qiang Wang
AU  - Lu O. Sun
AU  - Sarah P. Mitchell
AU  - Valera Vasioukhin
AU  - Richard L. Huganir
AU  - Alex L. Kolodkin
TI  - Dlg5 Regulates Dendritic Spine Formation and Synaptogenesis by Controlling Subcellular <em>N</em>-Cadherin Localization
AID  - 10.1523/JNEUROSCI.1280-14.2014
DP  - 2014 Sep 17
TA  - The Journal of Neuroscience
PG  - 12745--12761
VI  - 34
IP  - 38
4099  - http://www.jneurosci.org/content/34/38/12745.short
4100  - http://www.jneurosci.org/content/34/38/12745.full
SO  - J. Neurosci.2014 Sep 17; 34
AB  - Most excitatory synapses in the mammalian brain are formed on dendritic spines, and spine density has a profound impact on synaptic transmission, integration, and plasticity. Membrane-associated guanylate kinase (MAGUK) proteins are intracellular scaffolding proteins with well established roles in synapse function. However, whether MAGUK proteins are required for the formation of dendritic spines in vivo is unclear. We isolated a novel disc large-5 (Dlg5) allele in mice, Dlg5LP, which harbors a missense mutation in the DLG5 SH3 domain, greatly attenuating its ability to interact with the DLG5 GUK domain. We show here that DLG5 is a MAGUK protein that regulates spine formation, synaptogenesis, and synaptic transmission in cortical neurons. DLG5 regulates synaptogenesis by enhancing the cell surface localization of N-cadherin, revealing a key molecular mechanism for regulating the subcellular localization of this cell adhesion molecule during synaptogenesis.