MAGUKs: multifaceted synaptic organizers

Abstract

The PSD-95 family of proteins, known as MAGUKs, have long been recognized to be central building blocks of the PSD. They are categorized as scaffolding proteins, which link surface-expressed receptors to the intracellular signaling molecules. Although the four members of the PSD-95 family (PSD-95, PSD-93, SAP102, and SAP97) have many shared roles in regulating synaptic function, recent studies have begun to delineate specific binding partners and roles in plasticity. In the current review, we will highlight the conserved and unique roles of these proteins.

Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology

“…As the other family members, DLG1 contains multi-PDZ (PSD95/DLG/ZO-1) domains, a Src homology 3 interaction module and an enzymatically inert guanylate kinase domain. An accumulating body of evidence indicates that the modular organization and scaffolding properties of MAGUKs play crucial roles in important cellular processes and features of different cell types, like the regulation of signaling pathways which are linked to the control of tissue growth, differentiation, cell migration and cell architecture plasticity (Won et al, 2017).…”

Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs

“…Scaffold proteins serve as bridges linking the upstream glutamate receptors (i.e., NMDA-type glutamate receptors [NMDARs] and AMPA-type glutamate receptors [AMPARs]) with the downstream signaling complexes and cytoskeletons. Accordingly, spatial and temporal organization of scaffold protein-mediated protein complexes at the core of the PSD is pivotal for synaptic signaling and plasticity (Won et al, 2017;Zhu et al, 2016b). Mutations of genes encoding the PSD scaffold proteins have been frequently associated with various psychiatric disorders, including autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), intellectual disability (ID), and schizophrenia (Balan et al, 2013;Grant, 2012;Lelieveld et al, 2016;Pinto et al, 2010;Ting et al, 2012;Volk et al, 2015).…”

PSD-95 binding dynamically regulates NLGN1 trafficking and function

“…PKA | NLGN1 | phosphorylation | PSD-95 P SD-95, a member of membrane-associated guanylate kinases (MAGUK) protein family, is a major constituent of glutamatergic excitatory synapses and is specifically enriched at the postsynaptic density (PSD) (1). A large number of channels, receptors, and adhesion molecules bind to the PSD-95/Discs large/ZO-1 (PDZ), Src-homology-3, and guanylate kinase (GK) domains of PSD-95 (1,2). As a scaffolding protein at excitatory synapses, PSD-95 has been intensively studied vis a vis the organization of glutamatergic postsynaptic signaling.…”