Homer-1c/Vesl-1L Modulates the Cell Surface Targeting of Metabotropic Glutamate Receptor Type 1α: Evidence for an Anchoring Function

Ciruela, Francisco; Soloviev, Mikhail; Chan, Wai-Yee; McIlhinney, R. A. Jeffrey

doi:10.1006/mcne.1999.0808

Cited by 114 publications

(87 citation statements)

References 45 publications

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“…Coexpression of Flag-mGluR1␣ plus Homer 1c in HEK-293 cells resulted in a significant increase in plasma membrane localization of Flag-mGluR1␣, when compared with FlagmGluR1␣ alone (Fig. 4A), as has been previously shown (42). CaR does not contain the -PPSPFR-epitope, present near the carboxyl terminus of Group I mGluRs, which is required for interaction with the Homer EVH1 domain (69).…”

Section: Altered Surface Expression Of Car:mglur1␣ Heterodimers In Thsupporting

confidence: 80%

“…As a second test of plasma membrane localization of the CaR/mGluR heterodimers, we took advantage of the family of Homer/vesl proteins which interact with and specify subcellular localization of Group I mGluRs (40). In particular, Homer 1c has been shown both in vivo (41) and in vitro (42) to stabilize Group I mGluRs at the plasma membrane.…”

Section: Altered Surface Expression Of Car:mglur1␣ Heterodimers In Thmentioning

confidence: 99%

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Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Gama¹,

Wilt²,

Breitwieser³

2001

Journal of Biological Chemistry

143

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Section: Altered Surface Expression Of Car:mglur1␣ Heterodimers In Thsupporting

confidence: 80%

Section: Altered Surface Expression Of Car:mglur1␣ Heterodimers In Thmentioning

confidence: 99%

Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Gama¹,

Wilt²,

Breitwieser³

2001

Journal of Biological Chemistry

143

View full text Add to dashboard Cite

“…In summary, diffuse plasma membrane localization of mGluR1a/5 occurred when the receptor was expressed alone. Cotransfection of Homer-1a had no effect on the distribution of mGluR1a/5 (24-26, see also 27), while coexpression of Homer-1b/c either clustered the receptor at the plasma membrane (24,28) or decreased its surface expression by retarding mGluR1a/5 in the endoplasmatic reticulum (25,28, see also 26). The effect of Homer-1b on mGluR5 trafficking was abolished by point mutations in the Homer binding site of mGluR5 (i.e., PPSPF), which demonstrates that Homer-1b affects mGluR5 localization via a direct protein-protein interaction (25).…”

Section: Type I Metabotropic Glutamate Receptors (Mglurs)mentioning

confidence: 99%

Homer/Vesl Proteins and Their Roles in CNS Neurons

Ehrengruber

Kato

Inokuchi

et al. 2004

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“…CHO-GABAB-R1͞GABAB-R2 Cell Fractionation. CHO cell cultures were fractionated by using standard procedures (24) in the presence of protease inhibitors (Roche Molecular Biochemicals), and cytoplasmic extracts were analyzed by immunoblotting.…”

mentioning

confidence: 99%

“…On day 1 in vitro, the medium was replaced with fresh BNG medium [neurobasal medium (Gibco) containing 50 g͞ml gentamycin (26) and cytosine-␤-D-arabinofuranose (Sigma) to inhibit glial growth (5 M, days 1-7, 2.5 M thereafter)]. Nuclear fractionation was conducted by using standard techniques (24), and the nuclear and cytoplasmic fractions were analyzed by Western blotting and quantified.…”

mentioning

confidence: 99%

The GABA _B receptor interacts directly with the related transcription factors CREB2 and ATFx

White

McIllhinney²,

Wise³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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163

118

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␥-Aminobutyric acid type B (GABAB) receptors mediate the metabotropic actions of the inhibitory neurotransmitter GABA. These seven-transmembrane receptors are known to signal primarily through activation of G proteins to modulate the action of ion channels or second messengers. The functional GABAB receptor is made up of a heterodimer consisting of two subunits, GABAB-R1 and GABA B-R2, which interact via coiled-coil domains in their C-terminal tails. By using a yeast two-hybrid approach, we have identified direct interactions between the C-terminal tails of GABAB-R1 and GABAB-R2 with two related transcription factors, CREB2 (ATF4) and ATFx. In primary neuronal cultures as well in recombinant Chinese hamster ovary cells expressing GABAB receptors, CREB2 is localized within the cytoplasm as well as the nucleus. Activation of the GABAB receptor by the specific agonist baclofen leads to a marked translocation and accumulation of CREB2 from the cytoplasm into the nucleus. We demonstrate that receptor stimulation results in activation of transcription from a CREB2 responsive reporter gene. Such a signaling mechanism is unique among Family C G protein-coupled receptors and, in the case of the GABAB receptor and CREB2, may play a role in long-term changes in the nervous system. G ABA (␥-aminobutyric acid) is the major inhibitory neurotransmitter activating both ionotrophic GABA A and GABA C receptors as well as metabotropic GABA B receptors (1). GABA B receptors were originally identified pharmacologically (2) and couple through G proteins to Ca 2ϩ or K ϩ channels. Despite being recognized many years ago, the molecular nature of the GABA B receptor has been elucidated only recently (3-8). The initial GABA B ''receptor,'' GABA B -R1, was expression cloned by using a high-affinity antagonist and showed homology to Family C G protein-coupled receptors (GPCRs), such as metabotropic glutamate receptors, with a characteristically large extracellular N-terminal domain as well as a seven-transmembrane topology (3). However, when expressed recombinantly, GABA B -R1 failed to reproduce the expected agonist affinities (3, 5) and was not expressed at the cell surface (5, 9), suggesting that a component was lacking from GABA B -R1 for reconstitution of the functional receptor. Subsequent studies confirmed that a second distinct but related GPCR, GABA B -R2, heterodimerizes with GABA B -R1 to create the GABA B -receptor (4-8). Yeast two-hybrid (YTH) studies showed that the two receptors interact through a coiled-coil domain within their respective C-terminal tails (5, 7, 10), and in situ hybridization analysis showed colocalization of the two receptors (4, 5, 7, 10). The expressed heterodimer reproduced expected agonist pharmacology, and in the presence of GABA B -R2, GABA B -R1 was trafficked to the cell surface. Moreover, effector couplings to K ϩ and Ca 2ϩ channels have now been demonstrated by using the heterodimeric receptor (4,6,11,12).We previously used a YTH screen to identify GABA B -R2 as an interacting protein partner to G...

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Homer-1c/Vesl-1L Modulates the Cell Surface Targeting of Metabotropic Glutamate Receptor Type 1α: Evidence for an Anchoring Function

Cited by 114 publications

References 45 publications

Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Homer/Vesl Proteins and Their Roles in CNS Neurons

The GABA _B receptor interacts directly with the related transcription factors CREB2 and ATFx

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Homer-1c/Vesl-1L Modulates the Cell Surface Targeting of Metabotropic Glutamate Receptor Type 1α: Evidence for an Anchoring Function

Cited by 114 publications

References 45 publications

Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Homer/Vesl Proteins and Their Roles in CNS Neurons

The GABA B receptor interacts directly with the related transcription factors CREB2 and ATFx

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Product

Resources

About

The GABA _B receptor interacts directly with the related transcription factors CREB2 and ATFx