A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner

Kinoshita-Kawada, Mariko; Oberdick, John; Zhu, Michael X.

doi:10.1016/j.molbrainres.2004.09.007

Cited by 33 publications

(34 citation statements)

References 62 publications

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“…Although functional roles for the accessory protein AGS3 have been described in asymmetric cell division, neuronal plasticity and addiction, autophagy, polycystic kidney disease and renal injury, cardiovascular regulation, and metabolism (18 -28, 33), the data described in this study are the first to demonstrate a role for AGS3 in the regulation of chemokine responses in hematopoietic cells. Indeed, there are relatively few reports of GPCR signal modulation by GPR motif-containing proteins (21,28,(52)(53)(54)(55)(56), underscoring the significance of the current study, which, in contrast to the previous studies, makes use of primary cells obtained from genetic null (Gpsm1 Ϫ/Ϫ ) 3 mice.…”

Section: Discussionmentioning

confidence: 87%

“…As AGS3 GPR motifs compete with G␤␥ for G␣ i binding (12,29,72,73), one possibility is that AGS3 may "grab" free G␣ i -GDP prior to reassociation with G␤␥ and thus enhance or prolong G␤␥-regulated effector activation (13,16), and this hypothesis does have some support in the broader context of GPR proteins influencing G␣ i ␤␥ subunit interactions (12,23,24,26,33,(53)(54)(55)(56). The loss of AGS3 may thus lead to reduced chemokine-mediated G␤␥ signaling, which is the most likely explanation for the observed defects in Gpsm1 Ϫ/Ϫ leukocyte chemotaxis (Fig.…”

Section: Figure 5 Gpsm1mentioning

confidence: 99%

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Defective Chemokine Signal Integration in Leukocytes Lacking Activator of G Protein Signaling 3 (AGS3)

Branham‐O'Connor

Robichaux

Zhang

et al. 2014

Journal of Biological Chemistry

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Background: Roles for AGS3/Gpsm1 in the immune system are not defined. Results: Loss of AGS3 expression results in defective leukocyte chemotaxis, calcium mobilization, and ERK1/2 and Akt activation. Conclusion: AGS3 is required for efficient chemokine receptor signal integration. Significance: These studies extend the functional repertoire for AGS3 in the immune system, providing unexpected regulatory mechanisms for immune function.

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Section: Discussionmentioning

confidence: 87%

Section: Figure 5 Gpsm1mentioning

confidence: 99%

Defective Chemokine Signal Integration in Leukocytes Lacking Activator of G Protein Signaling 3 (AGS3)

Branham‐O'Connor

Robichaux

Zhang

et al. 2014

Journal of Biological Chemistry

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“…In HEK293 cells and X. laevis oocytes expressing GIRK1/2, LGN and GPR peptides activated basal Gβγ dependent K + currents and siRNA knockdown of LGN decreased basal GIRK currents in primary neuronal cultures (Wiser et al, 2006). The GPR containing protein Pcp2/L7 also modulated receptor regulation of Cav2.1 calcium channels expressed in X. laevis oocytes (Kinoshita-Kawada et al, 2004), but did not modify basal current. On the other hand, perfusion of a GPR peptide into AtT-20 cells did not activate basal native K + currents leading the authors to conclude that the GPR peptide could not dissociate G protein heterotrimers in cells (Webb et al, 2005).…”

Section: Gpr Proteins and Signal Processingmentioning

confidence: 97%

Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling

Blumer

Smrcka

Lanier

2007

Pharmacology & Therapeutics

122

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Signal processing via heterotrimeric G-proteins in response to cell surface receptors is a central and much investigated aspect of how cells integrate cellular stimuli to produce coordinated biological responses. The system is a target of numerous therapeutic agents, plays an important role in adaptive processes of organs, and aberrant processing of signals through these transducing systems is a component of various disease states. In addition to GPCR-mediated activation of G-protein signaling, nature has evolved creative ways to manipulate and utilize the Gαβγ heterotrimer or Gα and Gαβγ subunits independent of the cell surface receptor stimuli. In such situations, the G-protein subunits (Gα and Gαβγ) may actually be complexed with alternative binding partners independent of the typical heterotrimeric Gαβγ. Such regulatory accessory proteins include the family of RGS proteins that accelerate the GTPase activity of Gα and various entities that influence nucleotide binding properties and/or subunit interaction. The latter group of proteins includes receptor independent activators of G-protein signaling or AGS proteins that play surprising roles in signal processing. This review provides an overview of our current knowledge regarding AGS proteins. AGS proteins are indicative of a growing number of accessory proteins that influence signal propagation, facilitate cross talk between various types of signaling pathways and provide a platform for diverse functions of both the heterotrimeric Gαβγ and the individual Gα and Gαβγ subunits.

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“…Recently, detailed studies have demonstrated an interaction between Pcp2 and G-protein α (G α ) subunits, as well as the presence of a GoLoco motif. Some of these investigations have also identified putative phosphorylation sites at the C-terminus (Luo and Denker, 1999;Wanner et al, 2000;Kimple et al, 2002;Redd et al, 2002;Kinoshita-Kawada et al, 2004;Willard et al, 2006; Figure 1B). Given its highly conserved sequence, and relatively late start of expression between P4 and P8 (Nordquist et al, 1988;Oberdick et al, 1988;Vandaele et al, 1991;Wu and Cutting, 2001;Zhang et al, 2002), an important role has been suggested for Pcp2 in neuronal maturation and function.…”

Section: Introductionmentioning

confidence: 99%

Expression of a novel splicing variant of Pcp2 in closely related laboratory rodents

Przybyła

Nowacka-Chmielewska²,

Barski

2016

Genet. Mol. Res.

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ABSTRACT. Purkinje cell protein-2 (PCP2), also known as L7, is a member of the GoLoco protein family with highly cell-specific expression, being restricted to cerebellar Purkinje cells and retinal bipolar neurons in various species. However, its function in these tissues is unknown. Previous studies have suggested that PCP2 is a guanine nucleotide dissociation inhibitor, or a guanine nucleotide exchange factor. The Pcp2 gene is known to have many splice variants in both cerebellar Purkinje cells and retinal bipolar neurons. Here, we tested the hypothesis that a novel Pcp2 splice variant is conserved in closely related laboratory rodents (mice, rats, and hamsters). After analyzing alternative splicing of this gene in the Purkinje cells and retinas of these rodent species, we confirmed the presence of the novel longer transcript in mice. However, assessment of Pcp2 transcripts using polymerase chain reaction amplification of complementary DNA revealed this long splice variant containing the additional exon 3B to be absent from rats and hamsters. Thus, the novel Pcp2 transcript is particular to mouse cerebellar Purkinje cells and retinal bipolar neurons. It is likely to have arisen in this species, as a result of spontaneous mutation or de novo rearrangements. This gene presumably serves a very specific and, as yet, unknown function in the eyes and/or Purkinje cells of mice.

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A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner

Cited by 33 publications

References 62 publications

Defective Chemokine Signal Integration in Leukocytes Lacking Activator of G Protein Signaling 3 (AGS3)

Defective Chemokine Signal Integration in Leukocytes Lacking Activator of G Protein Signaling 3 (AGS3)

Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling

Expression of a novel splicing variant of Pcp2 in closely related laboratory rodents

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