Biology subjects

Warp, P. V.

Publications and source records attributed to Warp, P. V..

2 recordsLinked to original sources

bioRxiv2023

Control of microtubules in neuronal processes by profilin 1 and actomyosin

Microtubules, intermediate filaments, and actin are cytoskeletal polymer networks found within the cell. While each has unique functions, all the cytoskeletal elements must work together for cellular mechanics to be fully operative. This is achieved through crosstalk mechanisms whereby the different networks influence each other through signaling pathways and direct interactions. Because crosstalk can be complex, it is possible for perturbations in one cytoskeletal element to affect the others in ways that are difficult to predict. Here we investigated how long-term changes to the actin cytoskeleton affect microtubules and intermediate filaments. Reducing F-actin or actomyosin contractility increased acetylated microtubules and intermediate filament expression, with the effect being significantly more pronounced in neuronal processes. Changes to microtubules were completely reversible if F-actin and myosin activity is restored. Moreover, the altered microtubules in neuronal processes resulting from F-actin depletion caused significant changes to microtubule-based transport, mimicking phenotypes that are linked to neurodegenerative disease. Thus, defects in actin dynamics cause a compensatory response in other cytoskeleton components which profoundly alters cellular function.

cell biology↗

bioRxiv2019

Profilin 1 Controls the Assembly, Organization, and Dynamics of Leading Edge Actin Structures Through Internetwork Competition and Collaboration

How actin monomers are distributed to different networks remains poorly understood. One emerging concept is that the monomer pool is limited and heterogenous, causing biased assembly and internetwork competition. However, most knowledge regarding monomer distribution comes from studies where competing networks are discrete. In metazoans, many actin-based structures are complex, containing competing networks that overlap and are functionally interdependent. Addressing how monomers control the assembly and organization of these complex structures is critical to understanding how actin functions in cells. Here, we identify the monomer-binding protein profilin 1 (PFN1) as a major determinant of actin assembly, organization, and network homeostasis in mammalian cells. At the leading edge, PFN1 controls the localization and activity of the assembly factors Arp2/3 and Mena/VASP, with discrete stages of internetwork competition and collaboration occurring at different PFN1 concentrations. This causes substantial changes to leading edge actin architecture and the types of structures that form there.

cell biology↗