Principles of Unconventional Myosin Function and Targeting
Unconventional myosins are a superfamily of actin-based motors implicated in diverse cellular processes. In recent years, much progress has been made in describing their biophysical properties, and headway has been made into analyzing their cellular functions. Here, we focus on the principles that guide in vivo motor function and targeting to specific cellular locations. Rather than describe each motor comprehensively, we outline the major themes that emerge from research across the superfamily and use specific examples to illustrate each. In presenting the data in this format, we seek to identify open questions in each field as well as to point out commonalities between them. To advance our understanding of myosins' roles in vivo, clearly we must identify their cellular cargoes and the protein complexes that regulate motor attachment to fully appreciate their functions on the cellular and developmental levels.
Available from: Beata Fuchsova
- "Intriguingly, we found different nuclear myosins are recruited to different parts of viral replication centers, suggesting potentially unique functions for each myosin protein (Figs. 5 and 6). Surprisingly, neither NMI overexpression nor MVI ATPase inhibition caused significant alterations in viral replication (data not shown), however tools to probe the different structural and motor activities of the non-conventional myosins remain lacking[45,46]. Because nuclear actin, NMI and MVI are known general transcription factors and components of the preinitiation complex[37,38,47], recruitment of these proteins to sites of pol II probably facilitate transcription of the viral genome. On the other hand, we cannot exclude their potential role in viral DNA replication since both of these processes have been localized to the same centers. "
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ABSTRACT: Adenovirus serotypes have been shown to cause drastic changes in nuclear organization, including the transcription machinery, during infection. This ability of adenovirus to subvert transcription in the host cell facilitates viral replication. Because nuclear actin and nuclear myosin I, myosin V and myosin VI have been implicated as direct regulators of transcription and important factors in the replication of other viruses, we sought to determine how nuclear actin and myosins are involved in adenovirus infection. We first confirmed reorganization of the host's transcription machinery to viral replication centers. We found that nuclear actin also reorganizes to sites of transcription through the intermediate but not the advanced late phase of viral infection. Furthermore, nuclear myosin I localized with nuclear actin and sites of transcription in viral replication centers. Intriguingly, nuclear myosins V and VI, which also reorganized to viral replication centers, exhibited different localization patterns, suggesting specialized roles for these nuclear myosins. Finally, we assessed the role of actin in adenovirus infection and found both cytoplasmic and nuclear actin likely play roles in adenovirus infection and replication. Together our data suggest the involvement of actin and multiple myosins in the nuclear replication and late viral gene expression of adenovirus.
Copyright © 2015. Published by Elsevier Inc.
Available from: Audrey A Darabie
- "In particular, myosin motor proteins, which bind to and travel along actin filaments, control multiple processes in microvilli and stereocilia. Myosins have been implicated in transporting, anchoring and concentrating protein complexes and membrane vesicles, in exerting tension force on the plasma membrane and in influencing the structure of actin networks (reviewed by Krendel and Mooseker, 2005; Nambiar et al., 2010; Schwander et al., 2010; Hartman et al., 2011). One of the myosins that regulates actin-rich membrane protrusions in Drosophila and vertebrates is Myosin VIIA (Myo7A) (reviewed by El-Amraoui et al., 2008). "
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ABSTRACT: Microvilli and related actin-based protrusions permit multiple interactions between cells and their environment. How shape, length, and arrangement of microvilli are determined remains largely unclear. To address this issue and explore the cooperation of the two main components of a microvillus, the central F-actin bundle and the enveloping plasma membrane, we investigated expression and function of Myosin VIIA (Myo7A), which is encoded by crinkled (ck), and its interaction with cadherin Cad99C in the microvilli of the Drosophila follicular epithelium. Myo7A is present in the microvilli and terminal web of follicle cells, and associates with several other F-actin-rich structures in the ovary. Loss of Myo7A caused brush border defects and a reduction in the amount of the microvillus regulator Cad99C. We show that Myo7A and Cad99C form a molecular complex and that the cytoplasmic tail of Cad99C recruits Myo7A to microvilli. Our data indicate that Myo7A regulates the structure and spacing of microvilli, and interacts with Cad99C in vivo. A comparison of the mutant phenotypes suggests that Myo7A and Cad99C have co-dependent and independent functions in microvilli.
Available from: Gustavo Morrone Parfitt
- "The MLC is an essential component of this family that is responsible for cytoskeletal dynamics for communication, migration and cell division (Sellers, 2000; Redowicz, 2007; Hartman et al., 2011) Myosin has an important role in the processes related to structural stabilization and cellular dynamics, rendering the cell membrane resistant to potential deformations. Furthermore, myosin is involved in actin-enabled motor mechanisms and the organization of actin in the intracellular space (Hartman et al., 2011; Kneussel and Wagner, 2013). FLNa, a substrate of PAK, is also an important cellular structural component. "
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ABSTRACT: PAKs are a family of serine/threonine protein kinases activated by small GTPases of the Rho family, including Rac and Cdc42, and are categorized into group I (isoforms 1, 2 and 3) and group II (isoforms 4, 5 and 6). PAK1 and PAK3 are critically involved in biological mechanisms associated with neurodevelopment, neuroplasticity and maturation of the nervous system, and changes in their activity have been detected in pathological disorders, such as Alzheimer's disease, Huntington's disease and mental retardation. The group I PAKs have been associated with neurological processes due to their involvement in intracellular mechanisms that result in molecular and cellular morphological alterations that promote cytoskeletal outgrowth, increasing the efficiency of synaptic transmission. Their substrates in these processes include other intracellular signaling molecules, such as Raf, Mek and LIMK, as well as other components of the cytoskeleton, such as MLC and FLNa. In this review, we describe the characteristics of group I PAKs, such as their molecular structure, mechanisms of activation and importance in the neurobiological processes involved in synaptic plasticity.
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