Tubulin Post-translational Modifications: Potential Therapeutic Approaches to Heart Failure

Liu, Chang; Chen, Yu‐Wen; Xie, Yao; Xiang, Meixiang

doi:10.3389/fcell.2022.872058

Cited by 5 publications

(6 citation statements)

References 93 publications

(176 reference statements)

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“…Changes in microtubule dynamics are known to alter ion channel trafficking. In fact, an upregulation of the detyrosination of microtubules can induce HF ( Figure 3D ) ( 187 ). The detyrosination is a post-translational modification of tubulin, the protein building block of microtubules, which are essential components of the cytoskeleton.…”

Section: Ion Channel Trafficking Defect Contributes To the Developmen...mentioning

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 Trafficking Defect Contributes To the Developmen...mentioning

confidence: 99%

Ion channel trafficking implications in heart failure

Reisqs,

Qu,

Boutjdir

2024

Front. Cardiovasc. Med.

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“…Tubulin proteins are highly PTM (Akera, 2021; Garnham & Roll‐Mecak, 2012; Janke & Magiera, 2020; Joachimiak & Wloga, 2021; Moutin, Bosc, Peris, & Andrieux, 2021; Requena, Sanchez‐Madrid, & Martin‐Cofreces, 2021; Wattanathamsan & Pongrakhananon, 2021; Wloga, Joachimiak, & Fabczak, 2017) (Bar et al, 2022; C. Liu et al, 2022). Mass spectrometry‐based proteomics identified many PTM sites (N. Liu et al, 2015) (Figure S1).…”

Section: Ptm Of Tubulinsmentioning

confidence: 99%

“…MTs are involved in many physiological and pathological processes and regulated by microtubules‐associated proteins (MAPs) and enzymes that posttranslationally modify MTs (Akera, 2021; Atkins, Nicol, & Fassier, 2022; Bar, Popp, Bucher, & Mikhaylova, 2022; Caporizzo & Prosser, 2022; Forth & Kapoor, 2017; Janke & Magiera, 2020; Joachimiak & Wloga, 2021; Klena & Pigino, 2022; C. Liu, Chen, Xie, & Xiang, 2022). Small molecules that act on MTs, MAPs, and the enzymes also influence the functions of MTs (Warner, Li, & Li, 2022).…”

Section: Introductionmentioning

confidence: 99%

Microtubule‐associated proteins and enzymes modifying tubulin

Peng

Nakamura

2023

Cytoskeleton

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Microtubules (MTs) are essential for many cellular processes including establishment of cell shape and polarity, chromosome segregation, vesicle transport, and nuclear positioning. Human cells express 22 tubulin isoforms that have both overlapping and distinctive functions. Tubulins reversely polymerize to form cylindrical MTs, while MT‐associated proteins (MAPs), posttranslational modifications (PTMs), and mechanical forces regulate their functions. To help both tubulin researchers and medicinal chemists, this review article lists 489 MAPs, 43 known enzymes that mediate PTMs, and 306 drugs that influence the functions of MTs and MAPs and discusses recent microtubule research. Readers are able to sort the list based on name, size, functions, related human diseases, and date of discovery. The list also contains links to Uniprot and Protein Atlas databases to access further details such as protein structure, associated proteins, subcellular localization, expression levels in cells and tissues, mutations, and pathology. Because the microtubule cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target on MT and MAPs hold potential to treat these diseases and are also listed.

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“…These data suggest, that some changes on the surface or at the interface of PPI s are associated with posttranslational modifications. Due to their high therapeutic potential, MTs have been widely studied at different levels in animal systems (Čermák et al, 2020; Liu et al, 2022; Marchisella et al, 2016). Besides, plant systems are also considered valuable models for characterizing fundamental issues of MT organization and MAP interaction due to the considerable practical convenience, despite some differences between the two systems (Rayevsky et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

In silico induced effect of N‐ε‐lysine acetylation on microtubule stability and subsequent interaction of microtubule‐associated proteins

Rayevsky

Elijah

Sharifi

et al. 2023

Cell Biology International

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Plant systems have been considered valuable models for addressing fundamental questions of microtubule (MT) organization due to their considerable practical utility. Protein acetylation is a very common protein modification, and therate of acetylation can be modulated in cells in different biological states, and these changes can be detected at a molecular level. Here, we focused on K40, K112, and K394 residues as putative acetylation sites, which were shown to exist in both plants and mammals. Such residual effect of acetylation causes critical but unclear effect on MT stability. In turn, it was shown that acetylation indirectly affects the probability of interaction with different MAPs (Microtubule‐associated proteins). In a multiscale study using an all‐atom force field to reproduce several lattice‐forming elements found on the surface the microtubule, we assembled a fragment of a plant microtubule composed of nine tubulins and used it as a model object along with the existing human complex. Triplets of tubulins assembled in a lattice cell were then simulated for both human and plant protein complexes, using a coarse‐grained force field. We then analyzed the trajectories and identified some critical deformations of the MAP interaction surface. The initial coordinates were used to investigate the structural scenario in which autophagy‐related protein 8 (ATG8) was able to interact with the MT fragment.

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Tubulin Post-translational Modifications: Potential Therapeutic Approaches to Heart Failure

Cited by 5 publications

References 93 publications

Ion channel trafficking implications in heart failure

Ion channel trafficking implications in heart failure

Microtubule‐associated proteins and enzymes modifying tubulin

In silico induced effect of N‐ε‐lysine acetylation on microtubule stability and subsequent interaction of microtubule‐associated proteins

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