scholarly journals ER–mitochondria contacts: Actin dynamics at the ER control mitochondrial fission via calcium release

2017 ◽  
Vol 217 (1) ◽  
pp. 15-17 ◽  
Author(s):  
Janos Steffen ◽  
Carla M. Koehler
Keyword(s):  
Endoplasmic Reticulum ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Calcium Uptake ◽  
Calcium Release ◽  
Mitochondrial Fission ◽  
Actin Dynamics ◽  
Mitochondrial Division ◽  
Cell Biol ◽  
Important Player

The formin-like protein INF2 is an important player in the polymerization of actin filaments. In this issue, Chakrabarti et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201709111) demonstrate that INF2 mediates actin polymerization at the endoplasmic reticulum (ER), resulting in increased ER–mitochondria contacts, calcium uptake by mitochondria, and mitochondrial division.

scholarly journals Receptor-mediated Drp1 oligomerization on endoplasmic reticulum

2017 ◽  
Vol 216 (12) ◽  
pp. 4123-4139 ◽  
Author(s):  
Wei-Ke Ji ◽  
Rajarshi Chakrabarti ◽  
Xintao Fan ◽  
Lori Schoenfeld ◽  
Stefan Strack ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Actin Filaments ◽  
Mammalian Cells ◽  
Actin Polymerization ◽  
Mitochondrial Division ◽  
Multiple Factors ◽  
Guanosine Triphosphatase

Drp1 is a dynamin guanosine triphosphatase important for mitochondrial and peroxisomal division. Drp1 oligomerization and mitochondrial recruitment are regulated by multiple factors, including interaction with mitochondrial receptors such as Mff, MiD49, MiD51, and Fis. In addition, both endoplasmic reticulum (ER) and actin filaments play positive roles in mitochondrial division, but mechanisms for their roles are poorly defined. Here, we find that a population of Drp1 oligomers is associated with ER in mammalian cells and is distinct from mitochondrial or peroxisomal Drp1 populations. Subpopulations of Mff and Fis1, which are tail-anchored proteins, also localize to ER. Drp1 oligomers assemble on ER, from which they can transfer to mitochondria. Suppression of Mff or inhibition of actin polymerization through the formin INF2 significantly reduces all Drp1 oligomer populations (mitochondrial, peroxisomal, and ER bound) and mitochondrial division, whereas Mff targeting to ER has a stimulatory effect on division. Our results suggest that ER can function as a platform for Drp1 oligomerization, and that ER-associated Drp1 contributes to mitochondrial division.

scholarly journals Receptor-mediated Drp1 oligomerization on endoplasmic reticulum

2017 ◽  
Author(s):  
Wei-Ke Ji ◽  
Rajarshi Chakrabarti ◽  
Xintao Fan ◽  
Lori Schoenfeld ◽  
Stefan Strack ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Actin Polymerization ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Division ◽  
Knock Out ◽  
Multiple Factors ◽  
Latrunculin A

AbstractDrpl is a dynamin GTPase important for mitochondrial and peroxisomal division. Drp1 oligomerization and mitochondrial recruitment are regulated by multiple factors, including interaction with mitochondrial receptors such as Mff, MiD49, MiD51 and Fis. In addition, both endoplasmic reticulum (ER) and actin filaments play positive roles in mitochondrial division, but mechanisms for their roles are poorly defined. Here, we find that a population of Drp1 oligomers is ER-associated in mammalian cells, and is distinct from mitochondrial or peroxisomal Drp1 populations. Sub-populations of Mff and Fis1, which are tail-anchored proteins, also localize to ER. Drp1 oligomers assemble on ER, from which they can transfer to mitochondria. Suppression of Mff or inhibition of actin polymerization through the formin INF2 significantly reduces all Drp1 oligomer populations (mitochondrial, peroxisomal, ER-bound) and mitochondrial division, while Mff targeting to ER has a stimulatory effect on division. Our results suggest that ER can function as a platform for Drp1 oligomerization, and that ER-associated Drp1 contributes to mitochondrial division.SummaryAssembly of the dynamin GTPase Drp1 into constriction-competent oligomers is a key event in mitochondrial division. Here, Ji et al show that Drp1 oligomerization can occur on endoplasmic reticulum through an ER-bound population of the tail-anchored protein Mff.Abbreviations used in this paper: Drp1, dynamin-related protein 1; Fis1, mitochondrial fission 1 protein; INF2, inverted formin 2; KD, siRNA-mediated knock down; KI, CRISPR-mediated knock in; KO, CRISPR-mediated knock out; LatA, Latrunculin A; MDV, mitochondrially-derived vesicle; Mff, mitochondrial fission factor; MiD49 and MiD51, mitochondrial dynamics protein of 49 and 51 kDa; OMM, outer mitochondrial membrane; TA, tail-anchored.

scholarly journals Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics

2002 ◽  
Vol 156 (6) ◽  
pp. 1065-1076 ◽  
Author(s):  
Shoichiro Ono ◽  
Kanako Ono
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Biological Properties ◽  
Actin Dynamics ◽  
Background Suppression ◽  
Thin Filaments ◽  
Actin Organization ◽  
C Elegans ◽  
Filament Dynamics

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived from C. elegans, and showed that CeTM and UNC-60B bound to F-actin in a mutually exclusive manner. CeTM inhibited UNC-60B–induced actin depolymerization and enhancement of actin polymerization. Within isolated native thin filaments, actin and CeTM were detected as major components, whereas UNC-60B was present at a trace amount. Purified UNC-60B was unable to interact with the native thin filaments unless CeTM and other associated proteins were removed by high-salt extraction. Purified CeTM was sufficient to restore the resistance of the salt-extracted filaments from UNC-60B. In muscle cells, CeTM and UNC-60B were localized in different patterns. Suppression of CeTM by RNA interference resulted in disorganized actin filaments and paralyzed worms in wild-type background. However, in an ADF/cofilin mutant background, suppression of CeTM did not worsen actin organization and worm motility. These results suggest that tropomyosin is a physiological inhibitor of ADF/cofilin-dependent actin dynamics.

scholarly journals More than a mere supply of monomers: G-Actin pools regulate actin dynamics in dendritic spines

2017 ◽  
Vol 216 (8) ◽  
pp. 2255-2257 ◽  
Author(s):  
Katalin Schlett
Keyword(s):  
Plasma Membrane ◽  
Dendritic Spines ◽  
Actin Polymerization ◽  
Synaptic Activity ◽  
Actin Dynamics ◽  
Actin Monomer ◽  
Cell Biol ◽  
Local Enrichment

Synaptic activity reshapes the morphology of dendritic spines via regulating F-actin arborization. In this issue, Lei et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612042) reports a novel, G-actin–dependent regulation of actin polymerization within spine heads. They show that actin monomer levels are elevated in spines upon activity, with G-actin immobilized by the local enrichment of phosphatidylinositol (3,4,5)-triphosphate (PIP3) within the spine plasma membrane.

scholarly journals Insights into the evolution of regulated actin dynamics via characterization of primitive gelsolin/cofilin proteins from Asgard archaea

2020 ◽  
Vol 117 (33) ◽  
pp. 19904-19913 ◽  
Author(s):  
Caner Akıl ◽  
Linh T. Tran ◽  
Magali Orhant-Prioux ◽  
Yohendran Baskaran ◽  
Edward Manser ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filament ◽  
Calcium Binding ◽  
Mammalian Cells ◽  
Actin Polymerization ◽  
Calcium Release ◽  
Duplication Event ◽  
Cellular Level ◽  
Actin Dynamics

Asgard archaea genomes contain potential eukaryotic-like genes that provide intriguing insight for the evolution of eukaryotes. The eukaryotic actin polymerization/depolymerization cycle is critical for providing force and structure in many processes, including membrane remodeling. In general, Asgard genomes encode two classes of actin-regulating proteins from sequence analysis, profilins and gelsolins. Asgard profilins were demonstrated to regulate actin filament nucleation. Here, we identify actin filament severing, capping, annealing and bundling, and monomer sequestration activities by gelsolin proteins from Thorarchaeota (Thor), which complete a eukaryotic-like actin depolymerization cycle, and indicate complex actin cytoskeleton regulation in Asgard organisms. Thor gelsolins have homologs in other Asgard archaea and comprise one or two copies of the prototypical gelsolin domain. This appears to be a record of an initial preeukaryotic gene duplication event, since eukaryotic gelsolins are generally comprise three to six domains. X-ray structures of these proteins in complex with mammalian actin revealed similar interactions to the first domain of human gelsolin or cofilin with actin. Asgard two-domain, but not one-domain, gelsolins contain calcium-binding sites, which is manifested in calcium-controlled activities. Expression of two-domain gelsolins in mammalian cells enhanced actin filament disassembly on ionomycin-triggered calcium release. This functional demonstration, at the cellular level, provides evidence for a calcium-controlled Asgard actin cytoskeleton, indicating that the calcium-regulated actin cytoskeleton predates eukaryotes. In eukaryotes, dynamic bundled actin filaments are responsible for shaping filopodia and microvilli. By correlation, we hypothesize that the formation of the protrusions observed from Lokiarchaeota cell bodies may involve the gelsolin-regulated actin structures.

Unraveling a novel Rac1-mediated signaling pathway that regulates cofilin dephosphorylation and secretion in thrombin-stimulated platelets

Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 415-424 ◽  
Author(s):  
Dharmendra Pandey ◽  
Pankaj Goyal ◽  
Suman Dwivedi ◽  
Wolfgang Siess
Keyword(s):  
Signaling Pathway ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Specific Inhibitor ◽  
Class Ii ◽  
Actin Dynamics ◽  
Kinase C ◽  
Granule Secretion ◽  
Dependent Pathway ◽  
Calcineurin Inhibition

Abstract In platelets stimulated by thrombin to secrete and aggregate, cofilin is rapidly dephosphorylated leading to its activation. Cofilin by severing existing actin filaments and stimulating F-actin polymerization on newly created barbed ends dynamizes the actin cytoskeleton. We previously found that cofilin dephosphorylation is Ca2+-dependent and occurs upstream of degranulation in stimulated platelets. We report now in thrombin-stimulated platelets that Rac1 and class II PAKs (PAK4/5/6) were rapidly (within 5 seconds) activated, whereas PAK1/2 (class I PAKs) phosphorylation was slower. The Rac1-specific inhibitor NSC23766 blocked phosphorylation of class II PAKs, but not PAK1/2. Moreover, inhibition of the Ca2+/calmodulin-dependent phosphatase calcineurin inhibited Rac1 activation and class II PAKs phosphorylation. Prevention of Rac1 activation by calcineurin inhibition or NSC23766 also blocked cofilin dephosphorylation and platelet granule secretion indicating that a calcineurin/Rac1/class II PAKs pathway regulates cofilin dephosphorylation leading to secretion. We further found that PI3-kinases were activated downstream of Rac1, but were not involved in regulating cofilin dephosphorylation and secretion in thrombin-stimulated platelets. Our study unravels a Ca2+-dependent pathway of secretion in stimulated platelets as a signaling pathway linking Rac1 activation to actin dynamics: calcineurin→Rac1→class II PAKs→cofilin activation. We further demonstrate that this pathway is separate and independent of the protein kinase C (PKC) pathway mediating secretion.

scholarly journals A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Uri Manor ◽  
Sadie Bartholomew ◽  
Gonen Golani ◽  
Eric Christenson ◽  
Michael Kozlov ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Actin Assembly ◽  
Mitochondrial Division

Mitochondrial division, essential for survival in mammals, is enhanced by an inter-organellar process involving ER tubules encircling and constricting mitochondria. The force for constriction is thought to involve actin polymerization by the ER-anchored isoform of the formin protein inverted formin 2 (INF2). Unknown is the mechanism triggering INF2-mediated actin polymerization at ER-mitochondria intersections. We show that a novel isoform of the formin-binding, actin-nucleating protein Spire, Spire1C, localizes to mitochondria and directly links mitochondria to the actin cytoskeleton and the ER. Spire1C binds INF2 and promotes actin assembly on mitochondrial surfaces. Disrupting either Spire1C actin- or formin-binding activities reduces mitochondrial constriction and division. We propose Spire1C cooperates with INF2 to regulate actin assembly at ER-mitochondrial contacts. Simulations support this model's feasibility and demonstrate polymerizing actin filaments can induce mitochondrial constriction. Thus, Spire1C is optimally positioned to serve as a molecular hub that links mitochondria to actin and the ER for regulation of mitochondrial division.

scholarly journals Cofilin-mediated actin dynamics promotes actin bundle formation during Drosophila bristle development

2016 ◽  
Vol 27 (16) ◽  
pp. 2554-2564 ◽  
Author(s):  
Jing Wu ◽  
Heng Wang ◽  
Xuan Guo ◽  
Jiong Chen
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Model System ◽  
Actin Dynamics ◽  
Actin Network ◽  
Loss Of Function ◽  
Actin Bundle ◽  
Actin Bundles

The actin bundle is an array of linear actin filaments cross-linked by actin-bundling proteins, but its assembly and dynamics are not as well understood as those of the branched actin network. Here we used the Drosophila bristle as a model system to study actin bundle formation. We found that cofilin, a major actin disassembly factor of the branched actin network, promotes the formation and positioning of actin bundles in the developing bristles. Loss of function of cofilin or AIP1, a cofactor of cofilin, each resulted in increased F-actin levels and severe defects in actin bundle organization, with the defects from cofilin deficiency being more severe. Further analyses revealed that cofilin likely regulates actin bundle formation and positioning by the following means. First, cofilin promotes a large G-actin pool both locally and globally, likely ensuring rapid actin polymerization for bundle initiation and growth. Second, cofilin limits the size of a nonbundled actin-myosin network to regulate the positioning of actin bundles. Third, cofilin prevents incorrect assembly of branched and myosin-associated actin filament into bundles. Together these results demonstrate that the interaction between the dynamic dendritic actin network and the assembling actin bundles is critical for actin bundle formation and needs to be closely regulated.

scholarly journals Synaptic vesicle traffic is supported by transient actin filaments and regulated by PKA and NO

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicolas Chenouard ◽  
Feng Xuan ◽  
Richard W. Tsien
Keyword(s):  
Active Transport ◽  
Actin Filaments ◽  
Synaptic Vesicles ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Dynamic Allocation ◽  
Free Diffusion ◽  
Long Distance ◽  
Vesicle Traffic ◽  
Kinase A

Abstract Synaptic vesicles (SVs) can be pooled across multiple synapses, prompting questions about their dynamic allocation for neurotransmission and plasticity. We find that the axonal traffic of recycling vesicles is not supported by ubiquitous microtubule-based motility but relies on actin instead. Vesicles freed from synaptic clusters undergo ~1 µm bouts of active transport, initiated by nearby elongation of actin filaments. Long distance translocation arises when successive bouts of active transport were linked by periods of free diffusion. The availability of SVs for active transport can be promptly increased by protein kinase A, a key player in neuromodulation. Vesicle motion is in turn impeded by shutting off axonal actin polymerization, mediated by nitric oxide-cyclic GMP signaling leading to inhibition of RhoA. These findings provide a potential framework for coordinating post-and pre-synaptic strength, using retrograde regulation of axonal actin dynamics to mobilize and recruit presynaptic SV resources.

scholarly journals Regulation of Sodium Channel Activity by Capping of Actin Filaments

2003 ◽  
Vol 14 (4) ◽  
pp. 1709-1716 ◽  
Author(s):  
Ekaterina V. Shumilina ◽  
Yuri A. Negulyaev ◽  
Elena A. Morachevskaya ◽  
Horst Hinssen ◽  
Sofia Yu Khaitlina
Keyword(s):  
Plasma Membrane ◽  
Sodium Channel ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Channel Activity ◽  
Capping Protein ◽  
Channel Inactivation ◽  
Actin Capping Protein ◽  
Actin Capping

Ion transport in various tissues can be regulated by the cortical actin cytoskeleton. Specifically, involvement of actin dynamics in the regulation of nonvoltage-gated sodium channels has been shown. Herein, inside-out patch clamp experiments were performed to study the effect of the heterodimeric actin capping protein CapZ on sodium channel regulation in leukemia K562 cells. The channels were activated by cytochalasin-induced disruption of actin filaments and inactivated by G-actin under ionic conditions promoting rapid actin polymerization. CapZ had no direct effect on channel activity. However, being added together with G-actin, CapZ prevented actin-induced channel inactivation, and this effect occurred at CapZ/actin molar ratios from 1:5 to 1:100. When actin was allowed to polymerize at the plasma membrane to induce partial channel inactivation, subsequent addition of CapZ restored the channel activity. These results can be explained by CapZ-induced inhibition of further assembly of actin filaments at the plasma membrane due to the modification of actin dynamics by CapZ. No effect on the channel activity was observed in response to F-actin, confirming that the mechanism of channel inactivation does not involve interaction of the channel with preformed filaments. Our data show that actin-capping protein can participate in the cytoskeleton-associated regulation of sodium transport in nonexcitable cells.

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