Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Abstract

Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.

Structural basis of actin filament assembly and aging

“…After the exit of Pi, ADP-bound F-actin represents the 'aged' state of the filament, which can then be depolymerized back to G-actin. In vivo, this cyclic process is tightly regulated by a wide variety of actin-binding proteins (ABPs) that control the kinetics of actin turnover [8][9][10] . For instance, Gactin probably does not exist at significant concentrations as the uncomplexed monomer in vivo; instead it is essentially always bound to ABPs such as profilin and thymosin-b4 to prevent uncontrolled nucleation events 11,12 .…”

EVL Promotes Osteo-/Odontogenic Differentiation of Dental Pulp Stem Cells via Activating JNK Signaling Pathway

“…A large number of studies have shown that there is an inverse relationship between actin polymerization and adipogenesis, whereas there is a direct correlation between actin polymerization and osteogenesis [27,28,[42][43][44]. The dynamic nature of the actin cytoskeleton is determined by the actions of numerous actin-binding proteins, such as cofilin, profilin, CapZ, Arp2/ 3, and Ena/VASP family [45][46][47]. EVL, one of the Ena/VASP family involved in actin assembly and elongation, has been implicated in several types of cells with cell proliferation and differentiation by enhancing actin polymerization [37,39,[48][49][50].…”

Comparative Surfaceome Analysis of Clonal Histomonas meleagridis Strains with Different Pathogenicity Reveals Strain-Dependent Profiles

“…In the attenuated strain of H. meleagridis, the most prominent category of upregulated surface-associated proteins is cytoskeleton proteins, representing over one-third of the upregulated proteins in that strain. Comprising actin-related, actin-like and actin-associated proteins (AAPs) such as coronin, fibrin, and alpha-actinin, their action is focused in cytoskeleton remodeling and rearrangements [ 70 ]. It has been shown that these proteins are involved in the dynamic remodeling of the actin cytoskeleton, playing a role in multiple physiological processes such as cell migration, endocytosis, cytokinesis and cell morphogenesis [ 70 , 71 ].…”

“…Comprising actin-related, actin-like and actin-associated proteins (AAPs) such as coronin, fibrin, and alpha-actinin, their action is focused in cytoskeleton remodeling and rearrangements [ 70 ]. It has been shown that these proteins are involved in the dynamic remodeling of the actin cytoskeleton, playing a role in multiple physiological processes such as cell migration, endocytosis, cytokinesis and cell morphogenesis [ 70 , 71 ]. In agreement with this, attenuated histomonads demonstrate an amoeboid cellular morphology in vitro [ 72 ].…”