Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines

Shiraishi-Yamaguchi, Yoko; Sato, Yuichi; Sakai, Rieko; Mizutani, Akihiro; Knöpfel, Thomas; Mori, Nozomu; Mikoshiba, Katsuhiko; Furuichi, Teiichi

doi:10.1186/1471-2202-10-25

Cited by 63 publications

(77 citation statements)

References 36 publications

(62 reference statements)

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“…The loss of agonist-stimulated ERK1/2 phosphorylation by the mGluR1a-P1148L mutant is consistent with recent reports that Homer1a may contribute in part to the coupling of mGluR1a to the activation of ERK1/2 (Mao et al, 2005). The mechanism by which the P1148L mutation leads to increased filopodia formation is unclear, but Homer proteins may contribute to the regulation of actin dynamics through their interactions with the actin cytoskeletal regulatory proteins Cdc42 and Drebin (Shiraishi-Yamaguchi et al, 2009).…”

Section: Discussionsupporting

confidence: 75%

Somatic Mutations in GRM1 in Cancer Alter Metabotropic Glutamate Receptor 1 Intracellular Localization and Signaling

Esseltine

Willard²,

Wulur³

et al. 2013

Mol Pharmacol

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The activity of metabotropic glutamate receptors (mGluRs) is known to be altered as the consequence of neurodegenerative diseases such as Alzheimer, Parkinson, and Huntington disease. However, little attention has been paid to this receptor family's potential link with cancer. Recent reports indicate altered mGluR signaling in various tumor types, and several somatic mutations in mGluR1a in lung cancer were recently described. Group 1 mGluRs (mGluR1a and mGluR5) are coupled primarily to Gaq, leading to the activation of phospholipase C and to the formation of diacylglycerol and inositol 1,4,5-trisphosphate, leading to the release of Ca 21 from intracellular stores and protein kinase C (PKC) activation. In the present study, we investigated the intracellular localization and G protein-dependent and -independent signaling of eight GRM1 (mGluR1a) somatic mutations. Two mutants found in close proximity to the glutamate binding domain and cysteine-rich region (R375G and G396V) show both decreased cell surface expression and basal inositol phosphate (IP) formation. However, R375G shows increased ERK1/2 activation in response to quisqualate stimulation. A mutant located directly in the glutamate binding site (A168V) shows increased quisqualate-induced IP formation and, similar to R375G, increased ERK1/2 activation. Additionally, a mutation in the G protein-coupled receptor kinase 2/PKC regulatory region (R696W) shows decreased ERK1/2 activation, whereas a mutation within the Homer binding region in the carboxylterminal tail (P1148L) does not alter the intracellular localization of the receptor, but it induces changes in cellular morphology and exhibits reduced ERK1/2 activation. Taken together, these results suggest that mGluR1a signaling in cancer is disrupted by somatic mutations with multiple downstream consequences.

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Section: Discussionsupporting

confidence: 75%

Somatic Mutations in GRM1 in Cancer Alter Metabotropic Glutamate Receptor 1 Intracellular Localization and Signaling

Esseltine

Willard²,

Wulur³

et al. 2013

Mol Pharmacol

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“…However, no clear functional differences have been described between these two isoforms . Drebrin regulates neuronal actin dynamics and plasticity Kobayashi et al, 2004;Sekino et al, 2007;Shiraishi-Yamaguchi et al, 2009) binding to F-actin with high affinity, thereby competing with proteins such as fascin, a-actinin and tropomyosin Sasaki et al, 1996). Binding of drebrin to F-actin also facilitates the recruitment of other regulatory proteins such as gelsolin.…”

Section: Introductionmentioning

confidence: 99%

F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse

Pérez‐Martínez

Gordon-Alonso

Cabrero

et al. 2010

Journal of Cell Science

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SummaryThe adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding protein. Drebrin colocalizes with the chemokine receptor CXCR4 and F-actin at the peripheral supramolecular activation cluster in the immune synapse. Drebrin interacts with the cytoplasmic tail of CXCR4 and both proteins redistribute to the immune synapse with similar kinetics. Drebrin knockdown in T cells impairs the redistribution of CXCR4 and inhibits actin polymerization at the immune synapse as well as IL-2 production. Our data indicate that drebrin exerts an unexpected and relevant functional role in T cells during the generation of the immune response.

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“…For example, Shank interacts with a-fodrin (Böckers et al, 2001), cortactin (Hering and Sheng, 2003) and Abp1 (Qualmann et al, 2004), proteins that bind to F-actin. Homer proteins were also reported to bind F-actin (Shiraishi et al, 1999) and drebrin (Shiraishi-Yamaguchi et al, 2009). Interestingly, scaffolding proteins with mutations in their binding motifs to other PSD partners (for example disruption of GKAP-Shank interaction) can still be targeted to the postsynapse but are less stable and more dependent on F-actin, highlighting once again the importance of scaffold interactions with the cytoskeleton and emphasising the need to interact with scaffolding partners to stabilize the protein complexes in the PSD (Kuriu et al, 2006).…”

Section: Gkap-dlc2 Interaction Enhances Nmda Synaptic Currentsmentioning

confidence: 99%

GKAP-DLC2 interaction organizes postsynaptic scaffold complex to enhance synaptic NMDA receptor activity

Moutin

Raynaud

Fagni

et al. 2012

Journal of Cell Science

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SummaryAt glutamatergic brain synapses, scaffolding proteins regulate receptor location and function. The targeting and organization of scaffolding proteins in the postsynaptic density (PSD) is poorly understood, but it is known that a core protein of the glutamatergic receptor postsynaptic scaffold complex, guanylate-kinase-associated protein (GKAP) interacts with dynein light chain 2 (DLC2, also known as DYNLL2), a protein associated with molecular motors. In the present study, we combined BRET imaging, immunostaining and electrophysiological recording to assess the role of the GKAP-DLC2 interaction in the functional organization of the glutamatergic synapse. We found that GKAP-DLC2 interaction in dendritic spine stabilizes scaffolding protein expression at the PSD and enhances synaptic NMDA receptor activity. Moreover, the GKAP-DLC2 functional interaction is favored by sustained synaptic activity. These data identify a regulatory pathway of synaptic transmission that depends on activity-induced remodelling of the postsynaptic scaffold protein complex.

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Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines

Cited by 63 publications

References 36 publications

Somatic Mutations in GRM1 in Cancer Alter Metabotropic Glutamate Receptor 1 Intracellular Localization and Signaling

Somatic Mutations in GRM1 in Cancer Alter Metabotropic Glutamate Receptor 1 Intracellular Localization and Signaling

F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse

GKAP-DLC2 interaction organizes postsynaptic scaffold complex to enhance synaptic NMDA receptor activity

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