Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.

Published

Journal Article

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, Dlg5(LP), 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.

Full Text

Duke Authors

Cited Authors

  • Wang, S-HJ; Celic, I; Choi, S-Y; Riccomagno, M; Wang, Q; Sun, LO; Mitchell, SP; Vasioukhin, V; Huganir, RL; Kolodkin, AL

Published Date

  • September 2014

Published In

Volume / Issue

  • 34 / 38

Start / End Page

  • 12745 - 12761

PubMed ID

  • 25232112

Pubmed Central ID

  • 25232112

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.1280-14.2014

Language

  • eng