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Last update 08 May 2025

RAP1A

Last update 08 May 2025

Basic Info

Synonyms

C21KG, G-22K, GTP-binding protein smg p21A

+ [7]

Introduction

Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner. Together with ITGB1BP1, regulates KRIT1 localization to microtubules and membranes (PubMed:17916086). Plays a role in nerve growth factor (NGF)-induced neurite outgrowth. Plays a role in the regulation of embryonic blood vessel formation. Involved in the establishment of basal endothelial barrier function. Facilitates the progressive accumulation of CDH1 at mature desmosome junctions via cAMP-dependent signaling and its interaction with PKP3 (PubMed:25208567). May be involved in the regulation of the vascular endothelial growth factor receptor KDR expression at endothelial cell-cell junctions.

Drugs associated with RAP1A

CN118079002

Patent Mining

Target

RAP1A

Mechanism-

Active Org.

Academy of Military Medical Sciences

Originator Org.

Academy of Military Medical Sciences

Active Indication

Trauma, Nervous System

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RAP1A

100 Translational Medicine associated with RAP1A

0 Patents (Medical) associated with RAP1A

605

Literatures (Medical) associated with RAP1A

01 May 2025·Molecular Metabolism

The small GTPase Rap1 in POMC neurons regulates leptin actions and glucose metabolism

Article

Author: Kaneko, Kentaro ; Fukuda, Makoto ; Morozov, Alexei ; Lu, Weisheng ; Xu, Yong

The hypothalamic leptin-proopiomelanocortin (POMC) pathway is critical for regulating metabolism. POMC neurons in the arcuate nucleus respond to leptin and play a pivotal role in mediating energy and glucose balance. However, during diet-induced obesity (DIO), these neurons often develop resistance to exogenous leptin. Recently, the small GTPase Rap1 has been implicated as an inhibitor of neuronal leptin signaling; however, its specific role within POMC neurons remains unexplored. We generated tamoxifen-inducible, POMC neuron-specific Rap1 knockout mice to selectively delete both Rap1a and Rap1b isoforms in POMC neurons. By analyzing these mice through metabolic phenotyping, immunohistochemistry, and biochemical assays, we show that deleting Rap1a and Rap1b in POMC neurons prior to exposing the mice to a high-fat diet significantly prevented weight gain compared to control mice. Furthermore, while DIO mice with intact Rap1 failed to respond to exogenous leptin, genetically removing the Rap1 genes from DIO mice enhanced the ability of exogenous leptin to induce anorectic effects. Remarkably, acute deletion of Rap1 in POMC neurons of already obese mice improved hyperglycemia within one week, with minimal effect on body weight. This glycemic improvement was accompanied by improved glucose tolerance, enhanced insulin sensitivity, and improved cellular insulin signaling. Collectively, these findings suggest that loss of Rap1 in POMC neurons enhances leptin sensitivity, acutely improves glucose balance, and may offer a potential strategy to lower hyperglycemia in dietary obesity.

01 Apr 2025·JHEP Reports

RAP1A suppresses hepatic steatosis by regulating amino acid-mediated mTORC1 activation

Article

Author: Wang, Xiaobo ; Agarwal, Heena ; Wang, Yating ; Ozcan, Lale ; Tinsley, Brea

Background & AimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by triglyceride (TG) build-up in hepatocytes; however, our understanding of the underlying molecular mechanisms is limited. Here, we investigated the role of hepatic GTPase RAP1A in MASLD and its more progressive form, metabolic dysfunction-associated steatohepatitis (MASH).MethodsRAP1A was silenced or activated by AAV8-TBG-mediated gene expression or treating mice with a small molecule RAP1 activator (n = 4-12 per group). Primary hepatocytes were used to further probe the newly elucidated pathway. Liver samples from patients with MASH and control livers were analyzed for active RAP1A levels (n = 4 per group).ResultsActivation of hepatic RAP1A is suppressed in obese mice with MASLD and restoring its activity decreases liver steatosis. RAP1A activation lowers hepatic TG accumulation through decreasing sterol regulatory element-binding protein 1 (SREBP1) cleavage by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). The mechanism linking RAP1A activation to suppression of mTORC1 involves the lowering of membrane-bound amino acid transporters, which leads to reduced hepatocyte amino acid uptake, decreased intracellular amino acid levels, and inhibition of amino acid-mediated mTORC1 activation. Furthermore, we observed that active-RAP1A levels were decreased in mice fed a MASH-provoking diet (98% lower, p <0.01) and liver extracts from patients with MASH (86% lower, p <0.05). Accordingly, restoration of RAP1A activity in mice liver lowered liver fibrotic gene expression and prevented fibrosis formation, whereas RAP1A silencing promoted the progression of MASH.ConclusionsActivation of hepatic RAP1A lowers MASLD and MASH formation by suppressing amino acid-mediated mTORC1 activation and decreasing cleaved SREBP1. These data provide mechanistic insight into amino acid-mediated mTORC1 regulation and raise the possibility that hepatic RAP1A may serve as a mechanistic node linking obesity with MASLD and MASH.Impact and implicationsMetabolic dysfunction-associated liver pathologies are inadequately treated with currently available therapy. Here we demonstrate that the small GTPase RAS-associated protein 1A (RAP1A) protects against liver steatosis and fibrosis development by decreasing hepatocyte amino acid levels, which results in lower mTORC1 activity and SREBP1 cleavage. The results may present new targets against metabolic dysfunction related liver diseases.

01 Apr 2025·Acta Tropica

First molecular detection of Babesia bigemina in horseflies from Uruguay

Article

Author: Nascimento, Mariana Cavalcanti ; Riet-Correa, Franklin ; Campos, Vinicius Farias ; Krolow, Tiago Kütter ; Menchaca, Alejo ; Saravia, Anderson ; Rodrigues, Gratchela Dutra ; Morales, Diuliani Fonseca ; Nunes, Leandro Silva ; Dos Reis, Luana Ferreira Viana ; Lucas, Martín ; Krüger, Rodrigo Ferreira ; Domingues, William Borges ; Parodi, Pablo

Bovine babesiosis and anaplasmosis are primarily transmitted by the biological vector Rhipicephalus microplus. However, Anaplasma marginale may also be mechanically transmitted through the bites of haematophagous flies such as tabanids. While biological transmission by ticks is the predominant route for Babesia species, some reports suggest that mechanical transmission via fomites contaminated with merozoites may occur. Additionally, mechanical vectors such as tabanids may contribute to the spread of the disease. This study investigated the presence of Babesia bigemina and Babesia bovis in tabanids from three localities in Uruguay previously evaluated for the presence of A. marginale. We performed PCR amplification targeting the Rap-1a and gp45 genes, followed by Sanger sequencing. Our findings revealed that 4.21 % of the tabanids tested positive for B. bigemina, with the highest prevalence in Tacuarembó (28.57 %), followed by Paysandú (3.22 %) and Colonia (1.75 %). Dasybasis missionum from Tacuarembó, Poeciloderas lindneri from Paysandú, and Tabanus sp. from Colonia were positive. Additionally, a co-detection rate of 2 % with A. marginale was observed. These findings underscore the potential role of tabanids as vectors for Babesia bigemina, emphasizing the need for integrated vector control strategies in livestock management.

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RAP1A

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