The Rab GTPase in the heart: Pivotal roles in development and disease

Liu, Jiayi; Zheng, Xuanjun; Wu, Xiaoqian

doi:10.1016/j.lfs.2022.120806

Cited by 8 publications

(3 citation statements)

References 138 publications

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“…In cardiomyocytes, the transport of ion channels needs molecular motors and regulators. In the cytoplasm, the ion channel trafficking is coordinated by various Rab GTPases ( 154 ). Rab proteins belong to the largest family of small Ras-like GTPases.…”

Section: Ion Channel Traffickingmentioning

confidence: 99%

Ion channel trafficking implications in heart failure

Reisqs,

Qu,

Boutjdir

2024

Front. Cardiovasc. Med.

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Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%–2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survival of patients; however, despite these substantial improvements in treating HF, the incidence of HF is increasing rapidly, posing a significant burden to human health. The total cost of care for HF is USD 69.8 billion in 2023, warranting a better understanding of the mechanisms involved in HF. Among the most serious manifestations associated with HF is arrhythmia due to the electrophysiological changes within the cardiomyocyte. Among these electrophysiological changes, disruptions in sodium and potassium currents’ function and trafficking, as well as calcium handling, all of which impact arrhythmia in HF. The mechanisms responsible for the trafficking, anchoring, organization, and recycling of ion channels at the plasma membrane seem to be significant contributors to ion channels dysfunction in HF. Variants, microtubule alterations, or disturbances of anchoring proteins lead to ion channel trafficking defects and the alteration of the cardiomyocyte's electrophysiology. Understanding the mechanisms of ion channels trafficking could provide new therapeutic approaches for the treatment of HF. This review provides an overview of the recent advances in ion channel trafficking in HF.

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Section: Ion Channel Traffickingmentioning

confidence: 99%

Ion channel trafficking implications in heart failure

Reisqs,

Qu,

Boutjdir

2024

Front. Cardiovasc. Med.

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“…Rab GTPases (small GTPases such as the Rab3A/Rab27A system (Rab3A/27A system)) are an important family of proteins implicated in EV secretion. They have been demonstrated to be crucial for small EV (exosome) release, in charge of docking and fusion of multivesicular bodies with the plasma membrane [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Rab3A/Rab27A System Silencing Ameliorates High Glucose-Induced Injury in Podocytes

Martínez-Arroyo

Flores-Chova

Sanchez-Garcia

et al. 2023

Biology

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Diabetic nephropathy is a major complication in diabetic patients. Podocytes undergo loss and detachment from the basal membrane. Intra- and intercellular communication through exosomes are key processes for maintaining function, and the Rab3A/Rab27A system is an important counterpart. Previously, we observed significant changes in the Rab3A/Rab27A system in podocytes under glucose overload, demonstrating its important role in podocyte injury. We investigated the implication of silencing the Rab3A/Rab27A system in high glucose-treated podocytes and analysed the effect on differentiation, apoptosis, cytoskeletal organisation, vesicle distribution, and microRNA expression in cells and exosomes. For this, we subjected podocytes to high glucose and transfection through siRNAs, and we isolated extracellular vesicles and performed western blotting, transmission electron microscopy, RT-qPCR, immunofluorescence and flow cytometry assays. We found that silencing RAB3A and RAB27A generally leads to a decrease in podocyte differentiation and cytoskeleton organization and an increase in apoptosis. Moreover, CD63-positive vesicles experienced a pattern distribution change. Under high glucose, Rab3A/Rab27A silencing ameliorates some of these detrimental processes, suggesting a differential influence depending on the presence or absence of cellular stress. We also observed substantial expression changes in miRNAs that were relevant in diabetic nephropathy upon silencing and glucose treatment. Our findings highlight the Rab3A/Rab27A system as a key participant in podocyte injury and vesicular traffic regulation in diabetic nephropathy.

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“…Rab7 is a member of the Ras superfamily and plays a key role in the late stage of autophagy. Therefore, the dysfunction of Rab protein is linked to multiple human diseases, including cancer ( [30][31][32][33][34], infection [30,35,36], cardiac disease [37], and neurodegeneration [38][39][40][41][42][43]. In recent years, an increasing number of researchers [44][45][46][47][48][49][50] have focused on the role of Rab protein in the development of ALS.…”

Section: Introductionmentioning

confidence: 99%

Rab Geranylgeranyltransferase Subunit Beta as a Potential Indicator to Assess the Progression of Amyotrophic Lateral Sclerosis

Yang,

Xin,

Huo

et al. 2023

Brain Sciences

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Background: Currently, there is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder. Many biomarkers have been proposed, but because ALS is a clinically heterogeneous disease with an unclear etiology, biomarker discovery for ALS has been challenging due to the lack of specificity of these biomarkers. In recent years, the role of autophagy in the development and treatment of ALS has become a research hotspot. In our previous studies, we found that the expression of RabGGTase (low RABGGTB expression and no change in RABGGTA) is lower in the lumbar and thoracic regions of spinal cord motoneurons in SOD1G93A mice compared with WT (wild-type) mice groups, and upregulation of RABGGTB promoted prenylation modification of Rab7, which promoted autophagy to protect neurons by degrading SOD1. Given that RabGGTase is associated with autophagy and autophagy is associated with inflammation, and based on the above findings, since peripheral blood mononuclear cells are readily available from patients with ALS, we proposed to investigate the expression of RabGGTase in peripheral inflammatory cells. Methods: Information and venous blood were collected from 86 patients diagnosed with ALS between January 2021 and August 2023. Flow cytometry was used to detect the expression of RABGGTB in monocytes from peripheral blood samples collected from patients with ALS and healthy controls. Extracted peripheral blood mononuclear cells (PBMCs) were differentiated in vitro into macrophages, and then the expression of RABGGTB was detected by immunofluorescence. RABGGTB levels in patients with ALS were analyzed to determine their impact on disease progression. Results: Using flow cytometry in monocytes and immunofluorescence in macrophages, we found that RABGGTB expression in the ALS group was significantly higher than in the control group. Age, sex, original location, disease course, C-reactive protein (CRP), and interleukin-6 (IL-6) did not correlate with the ALS functional rating scale—revised (ALSFRS-R), whereas the RABGGTB level was significantly correlated with the ALSFRS-R. In addition, multivariate analysis revealed a significant correlation between RABGGTB and ALSFRS-R score. Further analysis revealed a significant correlation between RABGGTB expression levels and disease progression levels (ΔFS). Conclusions: The RABGGTB level was significantly increased in patients with ALS compared with healthy controls. An elevated RABGGTB level in patients with ALS is associated with the rate of progression in ALS, suggesting that elevated RABGGTB levels in patients with ALS may serve as an indicator for tracking ALS progression.

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The Rab GTPase in the heart: Pivotal roles in development and disease

Cited by 8 publications

References 138 publications

Ion channel trafficking implications in heart failure

Ion channel trafficking implications in heart failure

Rab3A/Rab27A System Silencing Ameliorates High Glucose-Induced Injury in Podocytes

Rab Geranylgeranyltransferase Subunit Beta as a Potential Indicator to Assess the Progression of Amyotrophic Lateral Sclerosis

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