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The functions of actin and its motor proteins myosins in the cytoplasm have been the subject of research for more than 100 years, but the existence and function of these proteins in the nucleus has been a matter of debate until recently. Recent data has clarified the role of actin and myosin molecules in controlling the dynamics of processes in the cell nucleus, chromatin organization and genome integrity. New microscopy techniques and the use of modified actin-binding probes have made it possible for the first time to directly visualize the polymerization of actin filaments in the nucleus of living cells. Here we discuss the processes that control the dynamic balance of actin and myosins between the nucleus and the cytoplasm, as well as the role of these proteins in the regulation of transcription, DNA repair, chromatin reorganization, tumor transformation and cell differentiation.

Myosin 1C is a monomeric myosin motor with a truncated tail domain. Such motors are referred as slow "tension sensors." Three isoforms of myosin 1C differ in short N-termed amino acid sequences, the functional differences between isoforms have not been elucidated. Myosin 1C isoform A was described as a diagnostic marker for prostate cancer, but its role in tumor transformation remains unknown. Based on data on the functions of myosin 1C, we hypothesized the potential role of myosin 1C isoforms in maintaining the tumor phenotype of prostate cancer cells. In our work, we showed that a decrease in the expression level of myosin 1C isoform C leads to an increase in the proliferative activity of prostate tumor cells., (© 2024. The Author(s).)

Rods and cones are photoreceptor neurons in the retina that are required for visual sensation in vertebrates, where proper protein localization and compartmentalization are critical for phototransduction and visual function. In human retinal diseases, improper protein transport to the outer segment (OS) or mislocalization of proteins to the inner segment (IS) could lead to impaired visual responses and photoreceptor cell degeneration, causing a loss of visual function. We showed involvement of an unconventional motor protein, MYO1C, in the proper localization of rhodopsin to the OS, where loss of MYO1C in a mammalian model caused mislocalization of rhodopsin to IS and cell bodies, leading to progressively severe retinal phenotypes. In this study, using modeling and docking analysis, we aimed to identify the protein-protein interaction sites between MYO1C and Rhodopsin to establish a hypothesis that a physical interaction between these proteins is necessary for the proper trafficking of rhodopsin and visual function., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Rods and cones are photoreceptor neurons in the retina that are required for visual sensation in vertebrates, wherein the perception of vision is initiated when these neurons respond to photons in the light stimuli. The photoreceptor cell is structurally studied as outer segments (OS) and inner segments (IS) where proper protein sorting, localization, and compartmentalization are critical for phototransduction, visual function, and survival. In human retinal diseases, improper protein transport to the OS or mislocalization of proteins to the IS and other cellular compartments could lead to impaired visual responses and photoreceptor cell degeneration that ultimately cause loss of visual function., Results: Therefore, studying and identifying mechanisms involved in facilitating and maintaining proper protein transport in photoreceptor cells would help our understanding of pathologies involving retinal cell degeneration in inherited retinal dystrophies, age-related macular degeneration, and Usher Syndrome., Conclusions: Our mini-review will discuss mechanisms of protein transport within photoreceptors and introduce a novel role for an unconventional motor protein, MYO1C, in actin-based motor transport of the visual chromophore Rhodopsin to the OS, in support of phototransduction and visual function.

Objective: The potential of brown adipose tissue (BAT) to influence energy homeostasis in animals and humans is encouraging as this tissue can increase fatty acid and glucose utilization to produce heat through uncoupling protein 1 (UCP1), but the actual mechanism of how the cell regulates glucose uptake is not fully understood. Myosin 1c (Myo1c) is an unconventional motor protein involved in several cellular processes, including insulin-mediated glucose uptake via GLUT4 vesicle fusion in white adipocytes, but its role in glucose uptake in BAT has not previously been investigated., Methods: Using the specific inhibitor pentachloropseudilin (PClP), a neutralizing antibody assay, and siRNA, we examined the role of Myo1c in mechanisms leading to glucose uptake both in vitro in isolated mouse primary adipocytes and in vivo in mice., Results: Our results show that inhibition of Myo1c removes insulin-stimulated glucose uptake in white adipocytes, while inducing glucose uptake in brown adipocytes, independent of GLUT4, by increasing the expression, translation, and translocation of GLUT1 to the plasma membrane. Inhibition of Myo1c leads to the activation of PKA and downstream substrates p38 and ATF-2, which are known to be involved in the expression of β-adrenergic genes., Conclusions: Myo1c is a PKA repressor and regulates glucose uptake into BAT., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: The human SH3 domain Binding Glutamic acid Rich Like 3 (SH3BGRL3) gene is highly conserved in phylogeny and widely expressed in human tissues. However, its function is largely undetermined. The protein was found to be overexpressed in several tumors, and recent work suggested a possible relationship with EGFR family members. We aimed at further highlighting on these issues and investigated SH3BGRL3 molecular interactions and its role in cellular migration ability., Results: We first engineered the ErbB2-overexpressing SKBR3 cells to express exogenous SH3BGRL3, as well as wild type Myo1c or different deletion mutants. Confocal microscopy analysis indicated that SH3BGRL3 co-localized with Myo1c and ErbB2 at plasma membranes. However, co-immunoprecipitation assays and mass spectrometry demonstrated that SH3BGRL3 did not directly bind ErbB2, but specifically recognized Myo1c, on its IQ-bearing neck region. Importantly, the interaction with Myo1c was Ca 2+ -dependent. A role for SH3BGRL3 in cell migration was also assessed, as RNA interference of SH3BGRL3 in MDA-MB-231 cells, used as a classical migration model, remarkably impaired the migration ability of these cells. On the other side, its over-expression increased cell motility., Conclusion: The results of this study provide insights for the formulation of novel hypotheses on the putative role of SH3BGRL3 protein in the regulation of myosin-cytoskeleton dialog and in cell migration. It could be envisaged the SH3BGRL3-Myo1c interaction as a regulation mechanism for cytoskeleton dynamics. It is well known that, at low Ca 2+ concentrations, the IQ domains of Myo1c are bound by calmodulin. Here we found that binding of Myo1c to SH3BGRL3 requires instead the presence of Ca 2+ . Thus, it could be hypothesized that Myo1c conformation may be modulated by Ca 2+ -driven mechanisms that involve alternative binding by calmodulin or SH3BGRL3, for the regulation of cytoskeletal activity., (© 2021. The Author(s).)

Unconventional myosins, linked to deafness, are also proposed to play a role in retinal cell physiology. However, their direct role in photoreceptor function remains unclear. We demonstrate that systemic loss of the unconventional myosin MYO1C in mice, specifically causes rhodopsin mislocalization, leading to impaired visual function. Electroretinogram analysis of Myo1c knockout ( Myo1c -KO) mice showed a progressive loss of photoreceptor function. Immunohistochemistry and binding assays demonstrated MYO1C localization to photoreceptor inner and outer segments (OS) and identified a direct interaction of rhodopsin with MYO1C. In Myo1c -KO retinas, rhodopsin mislocalized to rod inner segments (IS) and cell bodies, while cone opsins in OS showed punctate staining. In aged mice, the histological and ultrastructural examination of the phenotype of Myo1c -KO retinas showed progressively shorter photoreceptor OS. These results demonstrate that MYO1C is important for rhodopsin localization to the photoreceptor OS, and for normal visual function.