Cardiovascular Functions of Ena/VASP Proteins: Past, Present and Beyond

Benz, P.; Frömel, Timo; Laban, Hebatullah; Zink, Joana; Ulrich, Lea; Groneberg, Dieter; Boon, Reinier A.; Poley, Philip; Renné, Thomas; Wit, Cor de; Fleming, Ingrid

doi:10.3390/cells12131740

Cells

2023

DOI: 10.3390/cells12131740

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Cardiovascular Functions of Ena/VASP Proteins: Past, Present and Beyond

P. Benz

Timo Frömel

Hebatullah Laban

et al.

Abstract: Actin binding proteins are of crucial importance for the spatiotemporal regulation of actin cytoskeletal dynamics, thereby mediating a tremendous range of cellular processes. Since their initial discovery more than 30 years ago, the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family has evolved as one of the most fascinating and versatile family of actin regulating proteins. The proteins directly enhance actin filament assembly, but they also organize higher order actin networks and link kinase si… Show more

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Editorial: Evolution, emerging functions and structure of actin‐binding proteins, Volume II

Yin,

Kudryashov,

Zervas

et al. 2023

Front. Cell Dev. Biol.

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Editorial on the Research Topic Editorial: Evolution, emerging functions and structure of actin-binding proteins, Volume II Since the discovery of actin in the skeletal muscle in the 1940s, it has been found as a major cytoskeletal component mediating a wide range of cellular processes in all eukaryotic cells. In fulfilling these functions, actin is assisted by over 400 actin binding proteins (ABPs) (Gao and Nakamura, 2022), which can be generally divided into two classes: those that regulate the G-actin/ F-actin cycle and those that organize actin filaments in higher order structures (Yin et al., 2021;Rajan et al., 2023). The number of proteins involved in the actin cytoskeleton organization is even larger, as many interact with ABPs rather than actin itself. Such proteins can be called actincytoskeleton associated proteins (or actin-associated proteins, AAPs). Furthermore, the actual complexity of the actin cytoskeleton cannot be fully appreciated without realizing that many ABPs and AAPs are present in several isoforms, while their activity is altered, often dramatically and unpredictably, by numerous post-translational modifications (PTMs) (Yin and Schnoor, 2022). Still, numerous mutations in actin, ABPs, and AAPs distort the actin cytoskeleton's functionality, leading to genetic diseases that affect skeletal and heart muscle, immune, neural, bone, connective, and other tissues. Therefore, a not-so-uncommon opinion that the actin cytoskeleton is well understood is far from being accurate, as new functionalities of ABPs (e.g., processive pointed end actin polymerization; Kudryashova et al., 2022) are discovered regularly, while most are not sufficiently understood.Similarly, the therapeutic potential of ABPs has been barely tapped. In recent years, many ABPs have been considered as promising therapeutic targets in various diseases, such as cancer and asthma (Yin et al., 2019;Dahlstroem et al., 2023). For example, Wiskott-Aldrich syndrome protein (WASP) and WASP-interacting protein are tumor suppressors in T cell lymphoma; therefore, corresponding inhibitors could have a potent therapeutic effect (Menotti et al., 2019). Transgelin-2 regulates pulmonary resistance in asthma, and its agonists could aid in treating asthma (Yin et al., 2018). Outside of the cell, the diagnostic and therapeutic potential of plasma gelsolin (an ABP involved in Ca 2+ -dependent actin remodeling in the cell and actin sequestering in the extracellular space) in detecting inflammation and ameliorating consequences of generalized thrombosis have been revealed (Piktel et al., 2018;Zhang et al., 2023).

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Editorial: Evolution, emerging functions and structure of actin‐binding proteins, Volume II

Yin,

Kudryashov,

Zervas

et al. 2023

Front. Cell Dev. Biol.

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show abstract

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Cardiovascular Functions of Ena/VASP Proteins: Past, Present and Beyond

Cited by 1 publication

References 257 publications

Editorial: Evolution, emerging functions and structure of actin‐binding proteins, Volume II

Editorial: Evolution, emerging functions and structure of actin‐binding proteins, Volume II

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