Mechanisms of formin-mediated actin assembly and dynamics

Courtemanche, Naomi

doi:10.1007/s12551-018-0468-6

Cited by 124 publications

(125 citation statements)

References 146 publications

(321 reference statements)

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“…The nucleating function of Arp2/3 is further enhanced or activated by nucleation promoting factors such as Wiskott–Aldrich syndrome protein (WASP), Neural WASP (N‐WASP), and members of the WASP‐family verprolin‐homologous protein (WAVE) family (Kurisu & Takenawa, ; Machesky & Insall, ; Takenawa & Suetsugu, ). The actin nucleating formins, on the other hand, have been primarily implicated in driving the formation of parallel‐bundled actin filaments found in slender rod‐like protrusions known as filopodia (Breitsprecher & Goode, ; Courtemanche, ; Pollard, ). Upon nucleation, F‐actin filament growth is mediated by the actin polymerization machinery, which includes profilin, an actin‐binding protein initially proposed to sequester G‐actin monomers but now thought to promote the assembly of G‐actin into F‐actin (Alkam, Feldman, Singh, & Kiaei, ; Kang, Purich, & Southwick, ).…”

Section: The Critical Role Of the Growth Cone's Actin Cytoskeleton Inmentioning

confidence: 99%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and premyelinating OLGs, and during the process of active myelin wrapping, the forward movement of the leading edge of the myelin sheath's inner tongue along the axon.Almost all of these motile behaviors are driven by actin cytoskeletal dynamics initiated within a lamellipodial structure that is located at the tip of cellular OLG/OPC processes and is structurally as well as functionally similar to the neuronal growth cone. Accordingly, coordinated stoichiometries of actin filament (F-actin) assembly and disassembly at these OLG/OPC growth cones have been implicated in directing process outgrowth and guidance, and the initiation of myelination. Nonetheless, the functional importance of the OLG/OPC growth cone still remains to be fully understood, and, as a unique aspect of actin cytoskeletal dynamics, F-actin depolymerization and disassembly start to predominate at the transition from myelination initiation to myelin wrapping. This review provides an overview of the current knowledge about OLG/OPC growth cones, and it proposes a model in which actin cytoskeletal dynamics in OLG/OPC growth cones are a main driver for morphological transformations and motile behaviors. Remarkably, these activities, at least at the later stages of OLG maturation, may be regulated independently from the transcriptional gene expression changes typically associated with CNS myelination. K E Y W O R D Sactin cytoskeleton, growth cone, migration, myelination, oligodendrocyte

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Section: The Critical Role Of the Growth Cone's Actin Cytoskeleton Inmentioning

confidence: 99%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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“…The FH1 domain contains proline-rich motifs that interact with profilin-actin complex thereby recruiting actin monomers (Courtemanche and Pollard, 2012;Paul et al, 2008). The FH2 domains form dimers, which can nucleate actin filaments and function as processive caps at the filament plus (barbed) ends (Aydin et al, 2018;Courtemanche, 2018;Goode and Eck, 2007;Paul and Pollard, 2009). Combined action of FH1 and FH2 domains strongly accelerates filament growth.…”

Section: Introductionmentioning

confidence: 99%

The Formin Inhibitor, SMIFH2, Inhibits Members of the Myosin Superfamily

Nishimura

Shi

Zhang

et al. 2020

Preprint

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The small molecular inhibitor of formin FH2 domains, SMIFH2, is widely used in cell biological studies. It was selected in a chemical screen as a compound inhibiting formin-driven actin polymerization in vitro, but not polymerization of pure actin, and found to be active against several types of formins from different species (Rizvi et al., 2009). Here, in experiments with cultured fibroblasts, we found that SMIFH2 inhibits retrograde flow of myosin 2 filaments and contraction of stress fibers. We further checked the effect of SMIFH2 on non-muscle myosin 2A and skeletal muscle myosin 2 in vitro and found that SMIFH2 inhibits myosin ATPase activity and ability to translocate actin filaments in the in vitro motility assay. While inhibition of myosin 2A in vitro required somewhat higher concentration of SMIFH2 than inhibition of retrograde flow and stress fiber contraction in cells, inhibition of several other non-muscle myosin types, e.g. mammalian myosin 10, Drosophila myosin 7a and Drosophila myosin 5 by SMIFH2, was equally or more efficient than inhibition of formins. Since actin polymerization and myosin contractility are linked in many cytoskeleton processes, additional careful analysis is needed in each case when function of formins was proposed solely on the basis of experiment with SMIFH2.

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“…1A). Polymerase activity is thought to arise from formins ability to increase the binding frequency of profilin-actin (Courtemanche, 2018;Paul and Pollard, 2009;Vavylonis et al, 2006). Whether, however, filament growth in vivo is controlled at the level of binding is unknown.…”

Section: Introductionmentioning

confidence: 99%

Profilin and formin constitute a pacemaker system for robust actin filament growth

Funk

Merino

Venkova

et al. 2019

Preprint

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The actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration.

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Mechanisms of formin-mediated actin assembly and dynamics

Cited by 124 publications

References 146 publications

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

The Formin Inhibitor, SMIFH2, Inhibits Members of the Myosin Superfamily

Profilin and formin constitute a pacemaker system for robust actin filament growth

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