VNUT

Last update 08 May 2025

Basic Info

Synonyms

C20orf59, chromosome 20 open reading frame 59, FLJ23412

+ [5]

Introduction

Voltage-gated ATP nucleotide uniporter that can also transport the purine nucleotides ADP and GTP. Uses the membrane potential as the driving force to control ATP accumulation in lysosomes and secretory vesicles (PubMed:18375752, PubMed:23467297). By controlling ATP storage in lysosomes, regulates ATP-dependent proteins of these organelles (PubMed:35269509). Also indirectly regulates the exocytosis of ATP through its import into lysosomes in astrocytes and secretory vesicles such as adrenal chromaffin granules, mucin granules and synaptic vesicles (PubMed:18375752, PubMed:23467297).

100 Clinical Results associated with VNUT

100 Translational Medicine associated with VNUT

0 Patents (Medical) associated with VNUT

121

Literatures (Medical) associated with VNUT

01 Feb 2025·Molecular Psychiatry

Deletion of murine astrocytic vesicular nucleotide transporter increases anxiety and depressive-like behavior and attenuates motivation for reward

Article

Author: Pothos, Emmanuel N ; Quintana, Francisco J ; Stout, Randy F ; Li, Lingyun ; Lee, Hiu Ham ; Zhang, Qingchen ; Cai, Weikang ; Liu, Brian C ; Huang, Yuan ; Wong, Chun Wa ; Xue, Chang ; El Ouaamari, Abdelfattah ; Huang, Qian ; Liu, Tiemin ; Egholm, Julie ; Yang, Jeremy S ; Li, Allen ; Abuhasan, Yahia R ; Gutierrez-Vazquez, Cristina ; Ramos, Raddy L ; Kahn, C Ronald ; Volpe, Bryan ; Tang, Sharon ; Lee, Alyssa ; Lowell, Bradford B

Astrocytes are multi-functional glial cells in the central nervous system that play critical roles in modulation of metabolism, extracellular ion and neurotransmitter levels, and synaptic plasticity. Astrocyte-derived signaling molecules mediate many of these modulatory functions of astrocytes, including vesicular release of ATP. In the present study, we used a unique genetic mouse model to investigate the functional significance of astrocytic exocytosis of ATP. Using primary cultured astrocytes, we show that loss of vesicular nucleotide transporter (Vnut), a primary transporter responsible for loading cytosolic ATP into the secretory vesicles, dramatically reduces ATP loading into secretory lysosomes and ATP release, without any change in the molecular machinery of exocytosis or total intracellular ATP content. Deletion of astrocytic Vnut in adult mice leads to increased anxiety, depressive-like behaviors, and decreased motivation for reward, especially in females, without significant impact on food intake, systemic glucose metabolism, cognition, or sociability. These behavioral alterations are associated with significant decreases in the basal extracellular dopamine levels in the nucleus accumbens. Likewise, ex vivo brain slices from these mice show a strong trend toward a reduction in evoked dopamine release in the nucleus accumbens. Mechanistically, the reduced dopamine signaling we observed is likely due to an increased expression of monoamine oxidases. Together, these data demonstrate a key modulatory role of astrocytic exocytosis of ATP in anxiety, depressive-like behavior, and motivation for reward, by regulating the mesolimbic dopamine circuitry.

03 Jan 2025·Current Rheumatology Reviews

Clodronate: The Influence on ATP Purinergic Signaling

Article

Author: Molfetta, Luigi ; Saviola, Gianantonio ; Rosini, Sergio ; Rosini, Stefano

ATP is involved in numerous physiological functions, such as neurotransmission, modulation, and secretion, as well as in cell proliferation, differentiation, and death. While ATP serves an essential intracellular role as a source of energy, it behaves differently in the extracellular environment, where it acts as a signaling molecule capable of activating specific purinergic receptors (P2YRs and P2XRs) that modulate the response to ATP. Extracellular ATP signaling is a dynamic area of research, with particular interest in ATP’s effects on inflammatory conditions and pain modulation. Clodronate differs from other bisphosphonates that contain an amino group in their structure (N-BPs), and it is metabolized within osteoclasts into a toxic ATP analog, AppCCl2p, which causes mitochondrial dysfunction and osteoclast apoptosis. This characteristic differentiates Clodronate from N-BPs, as the latter act by interfering with the mevalonate pathway. Clodronate has demonstrated anti-inflammatory and analgesic activity in various bone and musculoskeletal diseases through mechanisms involving macrophages, neutrophils, peripheral nociceptors, and the central nervous system. ATP produced inside cells is accumulated within transport vesicles, where it penetrates via a VNUT channel and is then released extracellularly, playing an active role in acute and chronic inflammatory processes, neurotransmission of pain, and liver disease regulation. Clodronate influences these processes due to its strong inhibitory effect on VNUT-mediated ATP release. The aim of this review is to highlight the therapeutic potential offered by appropriate modulation of cellular ATP release and the inhibitory effects of Clodronate on the channel through which ATP penetrates transport vesicles.

01 Jan 2024·Protein & Peptide Letters

LINC01836 Promotes Colorectal Cancer Progression and Functions as ceRNA to Target SLC17A9 by Sponging miR-1226-3p

Article

Author: Ni, Hao ; Yu, Yue ; Kuang, Yuting ; Xu, Zhihua ; Sun, Wei

Background:Increasing evidence proves that long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of colorectal cancer. However, the function and molecular mechanism of LINC01836 in CRC are still unknown.Methods:The differentially expressed lncRNAs in colorectal cancer were obtained from the RNA sequencing data. The effects of LINC01836 on colorectal cancer cells were tested in in vitro experiments. The mechanism of LINC01836 action was investigated through western blot, RNA immunoprecipitation assay and luciferase reporter assay. Moreover, the xenograft mouse model was conducted to examine the effects of LINC01836 in vivo.Results:In this study, we showed that LINC01836 was significantly elevated in colorectal cancer tissues and cells. Elevated LINC01836 expression significantly correlated with larger tumor size, positive lymph node metastasis, distant metastasis, advanced tumor-node-metastasis (TNM) stage, and poor prognosis. Furthermore, decreased expression of LINC01836 repressed proliferation, migration, and invasion in vitro and vivo, and high LINC01836 expression displayed the opposite effect. Further analysis revealed that LINC01836 could regulate the expression of SLC17A9 by competing with miR-‐1226-3p. Furthermore, down-regulation of LINC01836 or increased expression of miR-‐1226-3p markedly reversed the effects of SLC17A9 overexpression on colorectal cancer cells.Conclusion:This study showed that LINC01836 regulated the expression of SLC17A9 through sponge miR-1226-3p by acting as a competitive endogenous RNA (ceRNA), promoted the progression of colorectal cancer, and suggested a new prognostic biomarker and potential cancer treatment target for colorectal cancer.

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VNUT

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