Last update 01 Nov 2024

GPSM1

Last update 01 Nov 2024

Basic Info

Synonyms

Activator of G-protein signaling 3, AGS3, DKFZP727I051

+ [3]

Introduction

Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction.

Drugs associated with GPSM1

AN-465

Target

GPSM1

Mechanism

GPSM1 modulators

Active Org.

Tessa Therapeutics Ltd [+1]

Originator Org.

Shanghai Jiao Tong University

Active Indication

Diabetes Mellitus [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AN-465 / 42243987

Target

GPSM1

Mechanism

GPSM1 inhibitors

Active Org.

Shanghai Jiao Tong University School of Medicine

Originator Org.

Shanghai Jiao Tong University School of Medicine

Active Indication

Diabetes Mellitus, Type 2 [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GPSM1

100 Translational Medicine associated with GPSM1

0 Patents (Medical) associated with GPSM1

Literatures (Medical) associated with GPSM1

01 Dec 2024·Clinical Proteomics

Identification of novel proteins in inflammatory bowel disease based on the gut-brain axis: a multi-omics integrated analysis

Article

Author: Xu, Yifeng ; Yan, Zhaoqi ; Liu, Liangji

BACKGROUNDThe gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear.MATERIALS AND METHODSIn this study, we aimed to investigate "novel proteins" underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn's disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes.RESULTSPWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD.CONCLUSIONThe two "novel proteins," SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

01 Aug 2024·eneuro

Adaptive Changes in Group 2 Metabotropic Glutamate Receptors Underlie the Deficit in Recognition Memory Induced by Methamphetamine in Mice

Article

Author: D'Errico, Giovanna ; Bruno, Valeria ; Nicoletti, Ferdinando ; Pittaluga, Anna ; Busceti, Carla Letizia ; Battaglia, Giuseppe ; Castaldi, Sonia ; Di Menna, Luisa ; Taddeucci, Alice ; Fornai, Francesco

Cognitive dysfunction is associated with methamphetamine use disorder (MUD). Here, we used genetic and pharmacological approaches to examine the involvement of either Group 2 metabotropic glutamate (mGlu2) or mGlu3 receptors in memory deficit induced by methamphetamine in mice. Methamphetamine treatment (1 mg/kg, i.p., once a day for 5 d followed by 7 d of withdrawal) caused an impaired performance in the novel object recognition test in wild-type mice, but not in mGlu2−/−or mGlu3−/−mice. Memory deficit in wild-type mice challenged with methamphetamine was corrected by systemic treatment with selectively negative allosteric modulators of mGlu2 or mGlu3 receptors (compounds VU6001966 and VU0650786, respectively). Methamphetamine treatment in wild-type mice caused large increases in levels of mGlu2/3 receptors, the Type 3 activator of G-protein signaling (AGS3), Rab3A, and the vesicular glutamate transporter, vGlut1, in the prefrontal cortex (PFC). Methamphetamine did not alter mGlu2/3-mediated inhibition of cAMP formation but abolished the ability of postsynaptic mGlu3 receptors to boost mGlu5 receptor-mediated inositol phospholipid hydrolysis in PFC slices. Remarkably, activation of presynaptic mGlu2/3 receptors did not inhibit but rather amplified depolarization-induced [3H]-D-aspartate release in synaptosomes prepared from the PFC of methamphetamine-treated mice. These findings demonstrate that exposure to methamphetamine causes changes in the expression and function of mGlu2 and mGlu3 receptors, which might alter excitatory synaptic transmission in the PFC and raise the attractive possibility that selective inhibitors of mGlu2 or mGlu3 receptors (or both) may be used to improve cognitive dysfunction in individuals affected by MUD.

15 Feb 2024·Journal of Cell Science

Properties of biomolecular condensates defined by Activator of G-protein Signaling 3

Article

Author: Lanier, Stephen M ; Vural, Ali

ABSTRACTActivator of G-protein signaling 3 (AGS3; also known as GPSM1), a receptor-independent activator of G-protein signaling, oscillates among defined subcellular compartments and biomolecular condensates (BMCs) in a regulated manner that is likely related to the functional diversity of the protein. We determined the influence of cell stress on the cellular distribution of AGS3 and core material properties of AGS3 BMCs. Cellular stress (oxidative, pHi and thermal) induced the formation of AGS3 BMCs in HeLa and COS-7 cells, as determined by fluorescent microscopy. Oxidative stress-induced AGS3 BMCs were distinct from G3BP1 stress granules and from RNA processing BMCs defined by the P-body protein Dcp1a. Immunoblots indicated that cellular stress shifted AGS3, but not the stress granule protein G3BP1 to a membrane pellet fraction following cell lysis. The stress-induced generation of AGS3 BMCs was reduced by co-expression of the signaling protein Gαi3, but not the AGS3-binding partner DVL2. Fluorescent recovery following photobleaching of individual AGS3 BMCs indicated that there are distinct diffusion kinetics and restricted fluidity for AGS3 BMCs. These data suggest that AGS3 BMCs represent a distinct class of stress granules that serve as a previously unrecognized signal processing node.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

GPSM1

Basic Info

Related

Analysis