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  • br Actin at presynapses br Conclusion Thanks to

    2024-05-14


    Actin at presynapses
    Conclusion Thanks to the recent discovery of rings, hotspots and trails, axonal cannabinoid receptor is back in the spotlight. These are exiting times for neuronal cell biologists armed with constantly improving labeling and imaging techniques to observe, quantify and perturb these structures. Future work will undoubtedly answer currently open questions: what are the molecular partners of these assemblies and how do they form? What are the relationships between these structures, and what regulates which actin structure is assembled depending on the time and place in the tight space of the axon? An interesting emerging model in non-neuronal cells is the competition between actin regulators for the formation of distinct structures (lamellipodia, filopodia, stress fibers, Burke et al., 2014; Davidson and Wood, 2016; Lomakin et al., 2015). This could apply to axonal actin, with the added complexity of a developmental regulation in neurons between dynamic structures and stable assemblies. Finally, the constantly evolving cellular imaging and manipulation capabilities will likely help shine a new light on presynaptic actin, allowing to reconcile the conflicting views of our current knowledge.
    Declarations of interest
    Acknowledgments Work in the NeuroCyto lab is supported by funding from the CNRS ATIP AO2016, and the project leading to this publication has received funding from the A*Midex Foundation of Aix-Marseille University, Pépinière d'Excellence 2017 to M.J.P., funded by socio-economics partners.
    Introduction The cytoskeleton is a primary structural component that determines the cell morphology. The cytoskeleton is also dynamic and changes its shape to play a role in many cellular functions. For example, filopodia and lamellipodia, dynamic cytoplasmic protrusions formed during cell migration, consist of thick bundles and orthogonal networks of actin filaments [1]. Networks of actin filaments aligned along cell boundaries provide mechanical support in epithelia [2]. A main constituent of the cytoskeleton is actin which is the most abundant protein in cells. The globular actin (G-actin) polymerizes into the filamentous actin (F-actin) in the presence of adenosine triphosphate (ATP) and divalent cations [3], [4], [5]. Both G-actin and F-actin interact with various actin-binding proteins (ABPs) and they assemble into higher-order structures. ABP α-actinin and fascin bind several actin filaments together to form thick bundles that are observed in filopodia and stress fibers, respectively [6], [7], [8]. Homogeneous network structures are organized by actin filaments cross-linked with ABP filamin [9]. The concentration of cross-linking ABP relative to actin determines the pore size of the actin network. Recent studies found that the mechanical responses of actin networks depended on the type of ABP as well as the constituent concentration [10], [11], [12]. The average length of actin filaments is regulated by a capping or severing ABP, such as gelsolin [4], [13]. Since actin in cells regulates organization of the cytoskeleton architecture according to the functional demands, investigating actin assembly in situ is essential to understanding cellular behaviors. However, it is difficult to probe the actin cytoskeleton cannabinoid receptor in cells due to the complexity of the cell and the lack of appropriate technique. Immuno-staining and transfection techniques using light microscopy have been widely used to detect actin in cells at high selectivity. However, the required processes of fixation and labeling can damage the cells and continuous monitoring of actin dynamics is limited with these techniques [14], [15]. A myopathy diagnostic tool employed label-free Raman spectroscopy to monitor muscle mutants by examining the biochemical responses of actin, myosin and other skeletal proteins [16]. Compared to optical measurements, electron microscopy allows the imaging of actin without a fluorescent tag at a higher spatial resolution of ∼ 50 pm [17], [18], [19]. However, it also requires a particular step in sample preparation, such as metal coating, and further requires a high vacuum condition for operation.