Developmental roles for Homer: more than just a pretty scaffold

Foa, Lisa; Gasperini, Robert

doi:10.1111/j.1471-4159.2008.05726.x

Cited by 45 publications

(28 citation statements)

References 77 publications

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“…By postnatal day 2 (P2), hippocampal excitatory synapses contain the majority of key PSD components involved in synaptic function and/or development (Petralia and others 2005) (Fig. 3), including mainly NR2B-NMDARs and SAP102, as well as GKAP, Shank, Homer, and Syn-GAP (Petralia and others 2005; Carlisle and others 2008; Foa and Gasperini 2009). …”

Section: Developmental Plasticitymentioning

confidence: 99%

“…They link metabotropic glutamate receptors (mGluRs) and various calcium channels (Fig. 2), both on nearby smooth ER (IP3 or ryanodine receptors) and on the surface membrane (including calcium-permeable glutamate receptors), and this arrangement may precisely regulate calcium levels in subregions of postsynaptic spines (Petralia and others 2001; Foa and Gasperini 2009). …”

Section: Glutamate Receptor Trafficking and Clustering At Synapsesmentioning

confidence: 99%

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MAGUKs, Synaptic Development, and Synaptic Plasticity

et al. 2011

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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.

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Section: Developmental Plasticitymentioning

confidence: 99%

Section: Glutamate Receptor Trafficking and Clustering At Synapsesmentioning

confidence: 99%

MAGUKs, Synaptic Development, and Synaptic Plasticity

et al. 2011

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“…Homer interacts with Shank-2, a multi-PDZ protein that binds PLCβ3, which promotes efficient coupling of Group I mGluRs to calcium signaling (Hwang et al, 2005). Finally, Homer couples mGluR signaling to Erk cascade activation (Mao et al, 2005) and promotes the development of dendritic spines (Foa & Gasperini, 2009). …”

Section: Gpcrs With Carboxy-terminal Pdz Recognition Motifsmentioning

confidence: 99%

Role of PDZ Proteins in Regulating Trafficking, Signaling, and Function of GPCRs: Means, Motif, and Opportunity

Romero

Zastrow

Friedman

2011

Advances in Pharmacology

145

119

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PDZ proteins, named for the common structural domain shared by the postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (DlgA), and zonula occludens-1 protein (ZO-1), constitute a family of 200–300 recognized members. These cytoplasmic adapter proteins are capable of assembling a variety of membrane-associated proteins and signaling molecules in short-lived functional units. Here, we review PDZ proteins that participate in the regulation of signaling, trafficking, and function of G protein-coupled receptors. Salient structural features of PDZ proteins that allow them to recognize targeted GPCRs are considered. Scaffolding proteins harboring PDZ domains may contain single or multiple PDZ modules and may also include other protein–protein interaction modules. PDZ proteins may impact receptor signaling by diverse mechanisms that include retaining the receptor at the cell membrane, thereby increasing the duration of ligand binding, as well as importantly influencing GPCR internalization, trafficking, recycling, and intracellular sorting. PDZ proteins are also capable of modifying the assembled complex of accessory proteins such as β-arrestins that themselves regulate GPCR signaling. Additionally, PDZ proteins may modulate GPCR signaling by altering the G protein to which the receptor binds, or affect other regulatory proteins that impact GTPase activity, protein kinase A, phospholipase C, or modify downstream signaling events. Small molecules targeting the PDZ protein-GPCR interaction are being developed and may become important and selective drug candidates.

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“…In addition, the postsynaptic density protein Homer plays a role in regulation of synaptic plasticity and neuronal development (Foa and Gasperini 2009) and alcohol sensitivity, in both flies and mammals (Urizar et al 2007; Cozzoli et al 2009). Other mutants include slowpoke , which encodes a large-conductance calcium-activated potassium channel (Cowmeadow et al 2005, 2006), and the transcription factors hangover (Scholz et al 2005) and dLmo/Beadex .…”

Section: Physiological Effects Of Alcoholmentioning

confidence: 99%

Genetics and genomics of alcohol sensitivity

2014

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Alcohol abuse and alcoholism incur a heavy socioeconomic cost in many countries. Both genetic and environmental factors contribute to variation in the inebriating effects of alcohol and alcohol addiction among individuals within and across populations. From a genetics perspective, alcohol sensitivity is a quantitative trait determined by the cumulative effects of multiple segregating genes and their interactions with the environment. This review summarizes insights from model organisms as well as human populations that represent our current understanding of the genetic and genomic underpinnings that govern alcohol metabolism and the sedative and addictive effects of alcohol on the nervous system.Electronic supplementary materialThe online version of this article (doi:10.1007/s00438-013-0808-y) contains supplementary material, which is available to authorized users.

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Developmental roles for Homer: more than just a pretty scaffold

Cited by 45 publications

References 77 publications

MAGUKs, Synaptic Development, and Synaptic Plasticity

MAGUKs, Synaptic Development, and Synaptic Plasticity

Role of PDZ Proteins in Regulating Trafficking, Signaling, and Function of GPCRs: Means, Motif, and Opportunity

Genetics and genomics of alcohol sensitivity

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