The molecular mechanisms driving the onset and metastasis of prostate cancer remain poorly understood. Actin, under the control of actin-binding proteins (ABPs), plays a crucial role in shaping the cellular cytoskeleton, which in turn supports the morphological alterations in normal cells, as well as the invasive spread of tumor cells. Previous research indicates that ABPs of various types serve distinct functions, and any disruptions in their activities could predispose individuals to prostate cancer. These ABPs are intricately implicated in the initiation and advancement of prostate cancer through a complex array of intracellular processes, such as severing, linking, nucleating, inducing branching, assembling, facilitating actin filament elongation, terminating elongation, and promoting actin molecule aggregation. As such, this review synthesizes existing literature on several ABPs linked to prostate cancer, including cofilin, filamin A, and fascin, with the aim of shedding light on the molecular mechanisms through which ABPs influence prostate cancer development and identifying potential therapeutic targets. Ultimately, this comprehensive examination seeks to contribute to the understanding and management of prostate diseases.

The actin cytoskeleton is one of the most important players in cell motility, adhesion, division, and functioning. The regulation of specific microfilament formation largely determines cellular functions. The main actin-binding protein in animal cells is tropomyosin (Tpm). The unique structural and functional diversity of microfilaments is achieved through the diversity of Tpm isoforms. In our work, we studied the properties of the cytoplasmic isoforms Tpm1.8 and Tpm1.9. The results showed that these isoforms are highly thermostable and differ in the stability of their central and C-terminal fragments. The properties of these isoforms were largely determined by the 6th exons. Thus, the strength of the end-to-end interactions, as well as the affinity of the Tpm molecule for F-actin, differed between the Tpm1.8 and Tpm1.9 isoforms. They were determined by whether an alternative internal exon, 6a or 6b, was included in the Tpm isoform structure. The strong interactions of the Tpm1.8 and Tpm1.9 isoforms with F-actin led to the formation of rigid actin filaments, the stiffness of which was measured using an optical trap. It is quite possible that the structural and functional features of the Tpm isoforms largely determine the appearance of these isoforms in the rigid actin structures of the cell cortex.

Intermediate filaments (IFs), being traditionally the least studied component of the cytoskeleton, have begun to receive more attention in recent years. IFs are found in different cell types and are specific to them. Accumulated data have shifted the paradigm about the role of IFs as structures that merely provide mechanical strength to the cell. In addition to this role, IFs have been shown to participate in maintaining cell shape and strengthening cell adhesion. The data have also been obtained that point out to the role of IFs in a number of other biological processes, including organization of microtubules and microfilaments, regulation of nuclear structure and activity, cell cycle control, and regulation of signal transduction pathways. They are also actively involved in the regulation of several aspects of intracellular transport. Among the intermediate filament proteins, vimentin is of particular interest for researchers. Vimentin has been shown to be associated with a range of diseases, including cancer, cataracts, Crohn\'s disease, rheumatoid arthritis, and HIV. In this review, we focus almost exclusively on vimentin and the currently known functions of vimentin intermediate filaments (VIFs). This is due to the structural features of vimentin, biological functions of its domains, and its involvement in the regulation of a wide range of basic cellular functions, and its role in the development of human diseases. Particular attention in the review will be paid to comparing the role of VIFs with the role of intermediate filaments consisting of other proteins in cell physiology.

Cryo-electron tomography (cryo-ET) has begun to provide intricate views of cellular architecture at unprecedented resolutions. Considerable efforts are being made to further optimize and automate the cryo-ET workflow, from sample preparation to data acquisition and analysis, to enable visual proteomics inside of cells. Here, we will discuss the latest advances in cryo-ET that go hand in hand with their application to the actin cytoskeleton. The development of deep learning tools for automated annotation of tomographic reconstructions and the serial lift-out sample preparation procedure will soon make it possible to perform high-resolution structural biology in a whole new range of samples, from multicellular organisms to organoids and tissues.

Early investigations of the neuronal actin filament cytoskeleton gave rise to the notion that, although growth cones exhibit high levels of actin filaments, the axon shaft exhibits low levels of actin filaments. With the development of new tools and imaging techniques, the axonal actin filament cytoskeleton has undergone a renaissance and is now an active field of research. This article reviews the current state of knowledge about the actin cytoskeleton of the axon shaft. The best understood forms of actin filament organization along axons are axonal actin patches and a submembranous system of rings that endow the axon with protrusive competency and structural integrity, respectively. Additional forms of actin filament organization along the axon have also been described and their roles are being elucidated. Extracellular signals regulate the axonal actin filament cytoskeleton and our understanding of the signaling mechanisms involved is being elaborated. Finally, recent years have seen advances in our perspective on how the axonal actin cytoskeleton is impacted by, and contributes to, axon injury and degeneration. The work to date has opened new venues and future research will undoubtedly continue to provide a richer understanding of the axonal actin filament cytoskeleton.

Nowadays, the population is still struggling with a post-COVID19 syndrome known as long COVID, including a broad spectrum of neurological problems. There is an urgent need for a better understanding and exploration of the mechanisms of coronavirus neurotropism. For this purpose, the neurotropic strain of mouse hepatitis virus (MHV-JHM) originating from the beta-coronavirus genus, the same as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been used. The role of the cytoskeleton during virus replication in neurons in vitro was determined to understand the mechanisms of MHV-JHM neuroinfection. We have described for the first time the changes of actin filaments during MHV-JHM infection. We also observed productive replication of MHV-JHM in neurons during 168 h p.i. and syncytial cytopathic effect. We discovered that the MHV-JHM strain modulated neuronal cytoskeleton during infection, which were manifested by: (i) condensation of actin filaments in the cortical layer of the cytoplasm, (ii) formation of microtubule cisternae structures containing viral antigen targeting viral replication site (iii) formation of tunneling nanotubes used by MHV-JHM for intercellular transport. Additionally, we demonstrated that the use of cytoskeletal inhibitors have reduced virus replication in neurons, especially noscapine and nocodazole, the microtubule shortening factors.

Both diastolic filling and systolic pumping of the heart are dependent on the passive stiffness characteristics of various mechanical elements of myocardium. However, the specific contribution from each element, including the extracellular matrix, actin filaments, microtubules, desmin intermediate filaments, and sarcomeric titin springs, remains challenging to assess. Recently, a mouse model allowing for precise and acute cleavage of the titin springs was used to remove one mechanical element after the other from cardiac fibers and record the effect on passive stiffness. It became clear that the stiffness contribution from each element is context-dependent and varies depending on strain level and the force component considered (elastic or viscous); elements do not act in isolation but in a tensegral relationship. Titin is a substantial contributor under all conditions and dominates the elastic forces at both low and high strains. The contribution to viscous forces is more equally shared between microtubules, titin, and actin. However, the extracellular matrix substantially contributes to both force components at higher strain levels. Desmin filaments may bear low stiffness. These insights enhance our understanding of how different filament networks contribute to passive stiffness in the heart and offer new perspectives for targeting this stiffness in heart failure treatment.

Cytoskeletal rearrangements and crosstalk between microtubules and actin filaments are vital for living organisms. Recently, an abundantly present microtubule polymerase, CKAP5 (XMAP215 homolog), has been reported to play a role in mediating crosstalk between microtubules and actin filaments in the neuronal growth cones. However, the molecular mechanism of this process is unknown. Here, we demonstrate, in a reconstituted system, that CKAP5 enables the formation of persistent actin bundles templated by dynamically instable microtubules. We explain the templating by the difference in CKAP5 binding to microtubules and actin filaments. Binding to the microtubule lattice with higher affinity, CKAP5 enables the formation of actin bundles exclusively on the microtubule lattice, at CKAP5 concentrations insufficient to support any actin bundling in the absence of microtubules. Strikingly, when the microtubules depolymerize, actin bundles prevail at the positions predetermined by the microtubules. We propose that the local abundance of available CKAP5-binding sites in actin bundles allows the retention of CKAP5, resulting in persisting actin bundles. In line with our observations, we found that reducing CKAP5 levels in vivo results in a decrease in actin-microtubule co-localization in growth cones and specifically decreases actin intensity at microtubule plus ends. This readily suggests a mechanism explaining how exploratory microtubules set the positions of actin bundles, for example, in cytoskeleton-rich neuronal growth cones.

Legumes enter into symbiotic associations with soil nitrogen-fixing rhizobia, culminating in the creation of new organs, root nodules. This complex process relies on chemical and physical interaction between legumes and rhizobia, including early signalling events informing the host legume plant of a potentially beneficial microbe and triggering the nodulation program. The great significance of this plant-microbe interaction rests upon conversion of atmospheric dinitrogen not accessible to plants into a biologically active form of ammonia available to plants. The plant cytoskeleton consists in a highly dynamic network and undergoes rapid remodelling upon sensing various developmental and environmental cues, including response to attachment, internalization, and accommodation of rhizobia in plant root and nodule cells. This dynamic nature is governed by cytoskeleton-associated proteins that modulate cytoskeletal behaviour depending on signal perception and transduction. Precisely localized cytoskeletal rearrangements are therefore essential for the uptake of rhizobia, their targeted delivery, and establishing beneficial root nodule symbiosis. This review summarizes current knowledge about rhizobia-dependent rearrangements and functions of the cytoskeleton in legume roots and nodules. General patterns and nodule type-, nodule stage-, and species-specific aspects of actin filaments and microtubules remodelling are discussed. Moreover, emerging evidence is provided about fine-tuning the root nodulation process through cytoskeleton-associated proteins. We also consider future perspectives on dynamic localization studies of the cytoskeleton during early symbiosis utilizing state of the art molecular and advanced microscopy approaches. Based on acquired detailed knowledge of the mutualistic interactions with microbes, these approaches could contribute to broader biotechnological crop improvement.

Tropomyosin (Tpm) is one of the most important partners of actin filament that largely determines its properties. In animal organisms, there are different isoforms of Tpm, which are believed to be involved in the regulation of various cellular functions. However, molecular mechanisms by which various Tpm cytoplasmic regulate of the functioning of actin filaments are still poorly understood. Here, we investigated the properties of Tpm2.1 and Tpm4.1 isoforms and compared them to each other and to more extensively studied Tpm isoforms. Tpm2.1 and Tpm4.1 were very similar in their affinity to F-actin, thermal stability, and resistance to limited proteolysis by trypsin, but differed markedly in the viscosity of their solutions and thermal stability of their complexes with F-actin. The main difference of Tpm2.1 and Tpm4.1 from other Tpm isoforms (e.g., Tpm1.6 and Tpm1.7) was their extremely low thermal stability as measured by the CD and DSC methods. We suggested the possible causes of this instability based on comparing the amino acid sequences of Tpm4.1 and Tpm2.1 with the sequences of Tpm1.6 and Tpm1.7 isoforms, respectively, that have similar exon structure.