title: MAGUKs, synaptic development, and synaptic plasticity.
abstract: MAGUKs are proteins that act as key scaffolds in surface complexes containing receptors, adhesion proteins, and various signaling molecules. These complexes evolved prior to the appearance of multicellular animals and play key roles in cell-cell intercommunication. A major example of this is the neuronal synapse, which contains several presynaptic and postsynaptic MAGUKs including PSD-95, SAP102, SAP97, PSD-93, CASK, and MAGIs. Here, they play roles in both synaptic development and in later synaptic plasticity events. During development, MAGUKs help to organize the postsynaptic density via associations with other scaffolding proteins, such as Shank, and the actin cytoskeleton. They affect the clustering of glutamate receptors and other receptors, and these associations change with development. MAGUKs are involved in long-term potentiation and depression (e.g., via their phosphorylation by kinases and phosphorylation of other proteins associated with MAGUKs). Importantly, synapse development and function are dependent on the kind of MAGUK present. For example, SAP102 shows high mobility and is present in early synaptic development. Later, much of SAP102 is replaced by PSD-95, a more stable synaptic MAGUK; this is associated with changes in glutamate receptor types that are characteristic of synaptic maturation.
authors.affiliation: National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Bethesda, MD 20892-8027, USA.
authors.forename: Chan-Ying
authors.initials: CY
authors.lastname: Zheng
authors.forename: Gail K
authors.initials: GK
authors.lastname: Seabold
authors.forename: Martin
authors.initials: M
authors.lastname: Horak
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C513314:DLG1 protein, human; C116869:DLG3 protein, human; C501444:DLG4 protein, human; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C106868:CASK kinases; D051528:Guanylate Kinases; C113338:MAGI1 protein, human