Profilin choreographs actin and microtubules in cells and cancer

Pimm, Morgan L; Hotaling, Jessica; Henty-Ridilla, Jessica L.

doi:10.1016/bs.ircmb.2020.05.005

Cited by 38 publications

(45 citation statements)

References 384 publications

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“…With this study, we emphasize profilin as a critical mediator of actin and microtubule cross-talk and extend the view of its role as a crucial component for cell architecture and behavior by its coordinated maintenance of actin and microtubule homeostasis as was recently discussed (39). We expect future studies to be directed to understand whether the interaction of profilin with either actin or components carrying the typical profilin-binding poly(L-proline)motif (26,27,28,29), or both is required for its inhibitory effect on centrosomal microtubule nucleation.…”

Section: Discussionsupporting

confidence: 70%

“…Tentatively, the role of profilin in the centrosome may be related to recent observations that also actin is a component of this organelle. Profilin-actin serves as source of actin for microfilament polymerization and as such co-operates with actin nucleation and elongation promoting proteins (26,27,28,29,33,39,40). A possible scenario is therefore that the loss of profilin results in less of actin polymerization in the centrosomal region in analogy with what was recently reported for the cell edge (41); as a consequence, less of steric hindrance (8,42) would reduce a possible space constrain for enhanced de novo microtubule nucleation.…”

Section: Discussionmentioning

confidence: 81%

“…Amazingly enough, profilin, therefore, operates in the molecular processes behind formation and growth of both actin filaments and microtubules; in the former case, it exert a positive role by providing actin as profilin-actin for polymer growth, whereas in the latter its function is to interfere with nucleation and elongation. Today, several proteins have been characterized as contributors to the connection and coordination of actin and microtubule organization (12,39), but to our knowledge, the duality of profilin in this respect is unique and puts profilin in a central position for the coupling of the actin and microtubule systems in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

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The actin regulator profilin 1 is functionally associated with the mammalian centrosome

et al. 2020

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Profilin 1 is a crucial actin regulator, interacting with monomeric actin and several actin-binding proteins controlling actin polymerization. Recently, it has become evident that this profilin isoform associates with microtubules via formins and interferes with microtubule elongation at the cell periphery. Recruitment of microtubule-associated profilin upon extensive actin polymerizations, for example, at the cell edge, enhances microtubule growth, indicating that profilin contributes to the coordination of actin and microtubule organization. Here, we provide further evidence for the profilin-microtubule connection by demonstrating that it also functions in centrosomes where it impacts on microtubule nucleation.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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The actin regulator profilin 1 is functionally associated with the mammalian centrosome

et al. 2020

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“…2). Profilins are abundant actin monomer sequestering proteins which can either augment or inhibit actin polymerization, depending on their biological context (28). We found that the siRNA-mediated knockdown of profilin 1 (Fig.…”

Section: Knockdowns Of Actin Monomers Sequestering and Capping Protein As Well As Treatment With Actin Monomers Sequestering Drugs Reversmentioning

confidence: 77%

Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives

Tee

Yong

et al. 2021

Preprint

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Deviations from mirror symmetry in the development of bilateral organisms are highly stereotypic and genetically predetermined, but their mechanisms are not sufficiently understood. At the cellular level, self-organization of the actin cytoskeleton results in chiral actin swirling, and cells in groups confined to micropatterns demonstrate chiral cell alignment. The relationship between individual and collective cell chirality is unclear, and molecular players involved remain essentially unidentified. Here, by screening major actin-associated proteins and deep-learning-based morphometric analysis of actin patterns, we found that knockdowns of specific actin polymerization regulators, such as mDia1, ARPC2, and cofilins 1&2, abolished chiral actin swirling, while depletion of profilin 1 and CapZβ, reversed its direction in an actin crosslinker α-actinin1-dependent manner. Analysis of these and other knockdowns and pharmacological treatments revealed a robust correlation between their effects on the chirality of individual cells and confined cell groups. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry.One Sentence SummaryCell chirality determined by specific regulators of actin polymerization drives left-right asymmetry emergence in cell groups

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“…Growing numbers of publications, studying patients and/or using cell or animal disease models, link profilins to various diseases: in cancers, PFN1 as well as PFN2 are reported to either act as tumor suppressors or possess oncogenic potential, depending on the studied cancer cell type (for review Pimm et al, 2020). In addition, some studies link PFN1 to a degenerative bone pathology known as Paget Disease (Merlotti et al, 2020;Scotto di Carlo et al, 2020), while others implicate this profilin isoform in vascular inflammation and atherosclerosis (see for review Pae and Romeo, 2014).…”

Section: Profilin 1 and Profilin 2a In Neurological Pathologiesmentioning

confidence: 99%

Profilin Isoforms in Health and Disease – All the Same but Different

Murk

Ornaghi

Schiweck

2021

Front. Cell Dev. Biol.

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Profilins are small actin binding proteins, which are structurally conserved throughout evolution. They are probably best known to promote and direct actin polymerization. However, they also participate in numerous cell biological processes beyond the roles typically ascribed to the actin cytoskeleton. Moreover, most complex organisms express several profilin isoforms. Their cellular functions are far from being understood, whereas a growing number of publications indicate that profilin isoforms are involved in the pathogenesis of various diseases. In this review, we will provide an overview of the profilin family and “typical” profilin properties including the control of actin dynamics. We will then discuss the profilin isoforms of higher animals in detail. In terms of cellular functions, we will focus on the role of Profilin 1 (PFN1) and Profilin 2a (PFN2a), which are co-expressed in the central nervous system. Finally, we will discuss recent findings that link PFN1 and PFN2a to neurological diseases, such as amyotrophic lateral sclerosis (ALS), Fragile X syndrome (FXS), Huntington’s disease and spinal muscular atrophy (SMA).

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Profilin choreographs actin and microtubules in cells and cancer

Cited by 38 publications

References 384 publications

The actin regulator profilin 1 is functionally associated with the mammalian centrosome

The actin regulator profilin 1 is functionally associated with the mammalian centrosome

Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives

Profilin Isoforms in Health and Disease – All the Same but Different

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