Dataset Information

Phosphoproteomic analysis supporting structural basis for GABAA receptor pi activation

ABSTRACT: GABAA receptors (GABAAR) are pentameric chloride channels comprising various combinations of different subunits that are activated by γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in vertebrates. we show here that GABRP chloride channel activity and ERK signaling is directly regulated by GABA binding to GABRP homopentamers. To help uncover GABRP’s link to ERK activity we used phosphoproteomic analysis to reveal signaling pathways regulated by GABA stimulation. Interestingly, and similar to metabotropic GABABRs, GABRP activation leads to phosphorylation of G-protein coupled pathways. These studies open new avenues for understanding GABRP signaling and additionally establish a foundation for conceptualizing the gating mechanism of related pentameric ligand gated ion channels. These studies open new avenues for understanding GABRP signaling and additionally establish a foundation for conceptualizing the gating mechanism of related pentameric ligand gated ion channels.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Wenxue Li

LAB HEAD: yansheng liu

PROVIDER: PXD044482 | Pride | 2026-01-05

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20230616_Yueyue_phos_BA_1.raw	Raw
	20230616_Yueyue_phos_BA_2.raw	Raw
	20230616_Yueyue_phos_BA_3.raw	Raw
	20230616_Yueyue_phos_BA_4.raw	Raw
	20230616_Yueyue_phos_BA_5.raw	Raw

Items per page:

1 - 5 of 12

Publications

GABAA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway.

Wang Yueyue Y Zhang Yalan Y Li Wenxue W Salovska Barbora B Zhang Jianan J Li Tongqing T Li Hengyi H Liu Yansheng Y Kaczmarek Leonard K LK Pusztai Lajos L Klein Daryl E DE

Molecular cell 20241205 1

The rare γ-aminobutyric acid type-A receptor (GABAAR) subunit π (GABRP) is highly expressed in certain cancers, where it stimulates growth through extracellular-regulated kinase (ERK) signaling by an uncharacterized pathway. To elucidate GABRP's signaling mechanism, we determined cryoelectron microscopy (cryo-EM) structures of GABRP embedded in native nanodiscs, both in the presence and absence of GABA. Structurally, GABRP homopentamers closely resemble heteropentameric GABAA</su ...[more]

PMID: 39642883

Similar Datasets

Project description:Voltage gated calcium channels play a central role in regulating the electrical and biochemical properties of neurons and muscle cells. Cells coordinate the expression of voltage gated calcium channels with the expression of other proteins that regulate membrane potential and calcium homeostasis. We report that the C-terminus of CaV 1.2, an L-type calcium channel (LTC) contains a C-terminal fragment that translocates to the nucleus and regulates transcription. This calcium channel associated transcription factor (CCAT) associates with transcriptional co-regulators such as p54nrb/NonO and binds to endogenous promoters. CCAT regulates the expression of gap junctions, sodium calcium exchangers, NMDA receptors, potassium channels and other proteins that regulate neuronal signaling. Electrical activity and developmental processes regulate the nuclear localization of CCAT, suggesting that the CCAT integrates information about the number of LTCs with information about the developmental history and electrical activity of a cell. These findings provide the first evidence that voltage gated calcium channels can directly activate transcription and suggest a novel mechanism linking voltage gated channels to the function and differentiation of excitable cells. Experiment Overall Design: The goal of these experiments was to identify the genes that are regulated by CCAT, a novel transcription factor derived from the C-terminus of CaV1.2. Neuro2A neuroblastoma cells were transfected with the last 503 AA of CaV1.2 which is full length CCAT (CCAT FL) or with the last 280 AA of CaV1.2, a form of CCAT that lacks the transcriptional activation domain (CCAT DTA). The mRNA from either CCAT FL or CCAT DTA expressing cells was hybridized to Agilent mouse genome microarrays along with mRNA from untransfected neuro2A cells (CCAT FL or DTA A series). Subsequent investigation revealed that transfection with the PA1 plasmid by itself increases the expression of some genes. To control for this effect we compared Neuro2A cells transfected with full length CCAT (in PA1) with Neuro2A cells transfectected with PA1 alone (CCAT FL B series). The microarray data was analyzed with the Rossetta Luminator gene expression data analysis system.

Dataset Information

Phosphoproteomic analysis supporting structural basis for GABAA receptor pi activation

Dataset's files

Publications

GABA<sub>A</sub> receptor π forms channels that stimulate ERK through a G-protein-dependent pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Phosphoproteomic analysis supporting structural basis for GABAA receptor pi activation

Dataset's files

Publications

GABA&lt;sub&gt;A&lt;/sub&gt; receptor π forms channels that stimulate ERK through a G-protein-dependent pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

GABA<sub>A</sub> receptor π forms channels that stimulate ERK through a G-protein-dependent pathway.