Cytoskeleton, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 5, 2024
The cellular functions that depend on the interactions of myosin motors and actin filaments are astonishingly diverse range from muscle contraction, non-muscle cell migration, intracellular transport, cytokinesis, adhesion, plasma membrane organization, morphogenesis, mechanotransduction to DNA organization repair (Busselman et al. 2024; Herzog Schappacher-Tilp 2023; Krendel Mooseker 2005; Quintanilla, Hammer, Beach Shahid-Fuente Toseland 2023). To perform this broad spectrum functions, mammalian cells use only six paralogs—four α-actin variants expressed in striated smooth cytoskeletal β- γ-actin (Khaitlina 2001; Simiczyjew 2017; Vedula Kashina 2018). In contrast, myosins constitute a large superfamily molecular have evolved into 79 classes across different taxa (Kollmar Mühlhausen 2017). It therefore appears complex repertoire contributes greatly complexity actomyosin functions. backbone is formed by heavy chain folds three distinct domains. motor domain, referred as head, converts energy ATP hydrolysis mechanical with filaments. neck domain binds one or more regulatory light chains connects C-terminal tail, which most part molecule interacts various cargoes. structure tail determines whether given single-headed monomer, double-headed dimer, multimer. Heavy conventional II consist long α-helical tails allow dimerization folding rod-like coiled coil further assemble thick bipolar arrangement molecules perfectly suited generate contractile forces pulling parallel (Billington 2013; Ojima 2019). unconventional contain two domains variety domains, but not capable forming (Fili Given myosin-dependent processes, it rather expected even small deviations native structures may severe consequences overall state humans other animals. Indeed, mutations both genes been implicated human diseases ranging cardiomyopathies myopathies skeletal breast skin cancer deafness (Coluccio 2020). issue begins memories Dr. Edward D. Korn Robert S. Adelstein, outstanding scientists who passed away 2024. For decades, Adelstein led studies cytoskeleton at National Heart, Lung Blood Institute Institutes Health Bethesda, MD. They participated scientific activities until very end, sharing their passion, knowledge, experience community. highly ordered sarcomeres crucial for precision actin−myosin force development. Caenorhabditis elegans, chains: A B present middle outer arms filament, respectively (Miller 1983). well established assembly maintenance require extensive within M-line proteins; however, exact mechanisms fully defined. results presented papers Pamela Hoppe's group shed necessary formation functional series carefully designed experiments, authors revealed unknown between proteins. By using chimeric constructs, localized regions rod responsible binding giant scaffolding protein UNC-89/obscurin zinc finger UNC-98/ZnF. These modification filament model (Almuhanna 2024). second paper (Schiller, Almuhanna, Hoppe 2023) reports discovery direct specific interaction UNC-82 kinase, orthologue NUAK1/2 kinase vertebrates. activity was found be important elongation, though phosphorylation site remains unknown. Three isoforms drive movement maintain tension cells, essential tissue an elegant study, Fowler colleagues progressed our understanding role IIA (NMIIA) contractility maturation differentiation ocular lens epithelial hexagonally shaped fiber cells. Experiments genetic knock-in mice heterozygous disease-linked missense demonstrated NMIIA indispensable alignment these fine, specialized (Islam involvement 1e (Myo1e) glomerular filtration nephron pathology has described Mira Krendel's group. This comprehensive review summarizes current knowledge presents hypotheses regarding function Myo1e physiology kidney. endothelial nephrons largely dependent cytoskeleton, playing role, judged effects MYO1E causing familial nephrotic syndrome (Liu Two address underlie hypertrophic cardiomyopathy (HCM), congenital heart disease associated least 11 genes, including encoding chain, chains, (Maron Maron 2013). work performed Danuta Szczesna-Cordary's lab focused HCM-linked mutation MYL2 gene ventricular (RLC). Using transgenic mice, showed phosphomimetic RLC can rescue phenotype establishing balance Super-relaxed Disordered Relaxed states heads (Liang Dietmar Manstein's compared cardiomyopathy-related ACTC1 cardiac β-myosin enzymatic activities. Their biochemical vitro analyzes line view interface forms structural basis performance (Greve Disorders also related dysregulation posttranslational modifications (MyHC). Advances quite new research area were reviewed Pinto his collaborators. types MyHC modifications, localizations, significance modulation physiological (Morales Tumor growth metastasis triggered alterations signaling cause changes shape, motility, extracellular environment. laboratory certain dynamics focal adhesions, process required invasiveness 4T1 (Garone study Samuel shape environment cutaneous squamous carcinoma. increased plays key recruitment tumor-promoting fibroblasts via cysteine-rich EGF-like 2 (CREDL2) paracrine stimulation. consequence phosphatase targeting subunit 1 (MYPT1), (MP), downstream Rho-ROCK pathway. Such mechanism seems affect tumors, those (Pittar An interesting authored Fumio Matsumura extends MYPT1-dependent pathways. well-known feature MYPT1 targets myosin, substrates (Kiss, Erdodi, Lontay evidence dynein intermediate (DIC) facilitating DIC dephosphorylation MP. turn activates transportation Rab7-containing vesicles dynein. As suggested authors, reduced expression contribute development pathological features compromising turnover some receptors (e.g., EGFR) (Matsumura Various methods reconstituted assemblies machinery being developed decipher collaborate division, migration. Papers describing progress factors affecting special issue. motility assays widely used studying propelled attached glass surface (Spudich Computational modeling done Taeyoon Kim's advanced experimental parameters lead homogeneous networks, flocks, bands, rings observed assay under conditions (Slater, Jung, Kim method enabling actin-activated S1 single-molecule level Månsson colleagues. Expression allows obtaining folded, protein, quantities limit applications. documented cross-linking recombinant EDC makes possible follow kinetics fluorescent TIRF microscopy. approach opens way high-throughput screening disease-related mutants available (Berg paper, Robinson discuss benefits challenges recently membrane-based reconstitution applied components cortex, actin-based built underneath (Waechtler description post-translational proteins, particular included summary, Special Issue "Myosins Myosin-Dependent Cell Processes" collection 13 aspects structure, interactions, regulation states. Along results, report advances methodology pertinent actin. Authors laboratories working actin, proteins accepted invitation create reporting recent, exciting results. addition, memoirs, John Hammer James Sellers, portrait lives groundbreaking discoveries great away. declare no conflicts interest.
Language: Английский