References:
This section is for me to keep track of all the important publications regarding actin including:
- Seminal papers : classic papers which would most definitely be used as citations in any actin related publication I may work on in the future.
- Reading inbox : papers regarding actin that I plan to read.
Seminal papers:
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Monomeric actin size, structure and interaction with other proteins. [@kabschAtomicStructureActin1990]
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F-actin atomic structure. [@holmesAtomicModelActin1990]
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Paper by Mullins and Pollard on Arp 2/3 interaction with actin: [@mullinsInteractionArp231998]
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Cryo-EM structure of Arp2/3 activation: [@chouMechanismActinFilament]
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A review on various actin NPFs: @campelloneNucleatorArmsRace2010
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Actin binding proteins:
- Effect of profilin on actin structure and physiological role of profilin in actin dynamics: @EffectsProfilinProfilactin1992
Reading inbox
- @vakhrushevaRoleActinbindingProteins2022
- A review on actin related proteins. The ones that I have read are the ones that were published before 2015. Might be a good idea to read a more recent one like this one.
- I really liked this nice figure which is a good visual summary of actin related proteins.
Actin filament nucleation and dynamics
Actin binding/interacting proteins
This table is generated by NotebookLM based on the sources I uploaded (listed at after the table):
| Protein/Component | Function/Molecular Mechanism | Associated Structural Organization | Interaction Partners | Regulatory Effect on Actin Assembly | Mechanical Properties (Inferred) | Source |
|---|---|---|---|---|---|---|
| Arp2/3 Complex | Nucleation and branching of actin filaments from sides of pre-existing filaments (dendritic nucleation) | Branched (dendritic) actin networks; Y-junctions | NPFs (Type I, WASP, WAVE, N-WASP, WASH, WHAMM, JMY, ActA), Arpin, GMF, Coronin, Gadkin, Actin filaments, Capping Protein (CP) | Activation (requires NPF and mother filament) | Force-generating capacity (elastic Brownian ratchet); branch points provide mechanical rigidity; stiffness scales as Lp/mesh_size4; high density increases drag force. | [1-5] |
| Capping Protein (CP) | Binds to and blocks the fast-growing (barbed) ends of actin filaments to terminate elongation | Branched networks; shortens filaments to increase density; necessary for symmetry breaking in actin shells | Actin barbed ends, V-1 (myotrophin), CARMIL2, Aip1, Arp2/3, VASP, Twinfilin | Inhibition (terminates elongation); qualitatively stimulates nucleation/motility by keeping monomer pool high (Monomer Gating) | Tuned force response via size-dependent Brownian Ratchet; regulates mesh size; makes filaments shorter and stiffer for efficient force generation; 2.7 nm gap required for binding; concentrations of 12.5-400 nM. | [1, 3-5] |
| Profilin-1 | Nucleotide exchange (ADP for ATP on G-actin); delivers monomers to barbed ends; sequesters monomers | Dynamic networks and bundles (stress fibers); essential for sustained motility | G-actin monomers, Polyproline domains of NPFs, Formin, VASP | Activation (promotes assembly at barbed ends); inhibits spontaneous nucleation and Arp2/3 activation by certain NPFs | Maintains polymerizable monomer pool for force-generating elongation; slows Dip1-mediated nucleation. | [1-6] |
| Formins (mDia1, mDia2, FMNL2) | Processive nucleation and elongation machine at barbed ends | Straight actin filaments; parallel bundles (filopodia) | Profilin, Rho-family GTPases (Cdc42, RhoA), APC | Activation (accelerates elongation up to 90 μM−1s−1) | High persistence length; generates piconewton forces; acts as a processive elongator to prevent buckling during growth. | [2, 3] |
| Myosin-II | Molecular motor generating contractile forces; actin filament gliding | Contractile fibers; antiparallel bundles (stress fibers, transverse arcs) | F-actin, Tropomyosin, α-actinin | Mixed (promotes network reorientation and contractility; induces disassembly via buckling) | Active spring; generates tension at focal adhesions; provides inward cortical pressure; stiffness increases 100-fold upon ATP depletion. | [2, 3] |
| ADF/Cofilin | Severing and depolymerization/disassembly of actin filaments (targets ADP-actin) | Network turnover zones (back of lamellipodium) | ADP-actin filaments, Aip1, GMF, CAP/Srv2 | Inhibition (disassembly); qualitative activation (generates new barbed ends for growth and monomer recycling) | Decreases persistence length from 10 μm to 2 μm (increases flexibility); fluidizes network (shock absorber/dashpot); triggers stochastic macroscopic fragmentation. | [2-4, 7, 8] |
| Myosin-I (Myo1d, Myo1c, Myo1e) | Membrane-anchored motor; pushes actin filaments via power stroke | Sparser branched actin networks (thinning) | Anionic phospholipids, Arp2/3 complex, NPFs | Modulation (reduces branching rate; increases growth efficiency) | Exerts repulsive force; power stroke sufficient to fracture actin shells and break symmetry; enhances network pushing force capacity. | [9] |
| Myotrophin/V-1 | High-affinity competitive inhibitor of Capping Protein (CP); sterically blocks F-actin binding site | Promotes longer filaments; diffuse, disorganized actin clouds (when CP is inhibited) | Capping Protein (CP), CARMIL | Activation of assembly (by inhibiting CP); reduces nucleation rate | Decreases actin network density; prevents CP recruitment; inhibition at 5 μM; microMolar cytoplasmic concentrations. | [1, 5] |
| α-actinin | Antiparallel dimer bundling actin filaments | Contractile fibers; bundles; networks | F-actin, Myosin, Vinculin | Qualitative Activation (organizes networks) | Crosslinks filaments 35 nm apart; rupture forces of 40-80 pN; contributes to cell mechanosensitivity and stiffness. | [2, 3] |
| Fascin | Bundling actin filaments into parallel arrays | Parallel bundles (filopodia) | F-actin, α-actinin, Ena/VASP | Qualitative Activation (stabilizes bundles) | Tightly packs filaments (8 nm apart); increases bundle stiffness (stiffness scales with N2 if crosslinked). | [2, 3] |
| VASP / Ena family | Antagonizes Capping Protein; promotes filament elongation and bundling | Parallel bundles; filopodia | Actin filaments, ActA, Profilin, Capping Protein | Suppresses dendritic nucleation; promotes linear filament growth | Increases persistence length; aligns filaments; reduces branch density in comet tails. | [4, 7] |
| CARMIL (CPI-motif protein) | Allosteric inhibitor of CP capping; promotes V-1 dissociation from CP | Asymmetric actin tails (local activation of CP at membranes) | Capping Protein (CP), V-1 | Local activation of CP by displacing V-1; high levels directly inhibit CP | Recruits CP to surfaces; optimizes actin assembly mass near membranes; biphasic effect based on concentration. | [5] |
| ActA | Nucleation Promoting Factor (NPF); activates Arp2/3 complex | Actin comet tails; spherically symmetrical actin shells | Arp2/3 complex, VASP | Activation of dendritic nucleation at surfaces | Tethers filaments to surfaces; force-velocity relation for Listeria is biphasic. | [4, 7] |
| Thymosin-β4 (Tβ4) | Sequesters G-actin monomers | Regulates available monomer pool | G-actin monomers | Inhibition (prevents nucleation/polymerization) | Inverse correlation with stiffness; high Tβ4 levels lead to softer cells due to fewer stress fibers. | [2] |
| Dip1 | Arp2/3 complex activator that functions without preformed filaments | Linear/unbranched actin filaments (seed filaments) | Arp2/3 complex | Initiates branched assembly by providing the first ‘seed’ filaments | Serves as master timer/switch for endocytic patch assembly; more potent activator than Wsp1. | [6] |
[1] Li et al. - 2022 - The molecular mechanism of load adaptation by branched actin networks [2] Vakhrusheva et al. - 2022 - Role of actin-binding proteins in the regulation of cellular mechanics [3] blanchoin-et-al-2014-actin-dynamics-architecture-and-mechanics-in-cell-motility [4] Akin and Mullins - 2008 - Capping Protein Increases the Rate of Actin-Based Motility by Promoting Filament Nucleation by the A [5] Mooren et al. - 2024 - Reconstitution of Arp23-Nucleated Actin Assembly with Proteins CP, V-1 and CARMIL [6] Wagner et al. - 2013 - Dip1 Defines a Class of Arp23 Complex Activators that Function without Preformed Actin Filaments [7] Mogilner and Oster - 2003 - Force Generation by Actin Polymerization II The Elastic Ratchet and Tethered Filaments [8] Actin dynamics, architecture, and mechanics in cell motility [9] Xu et al. - Myosin-I synergizes with Arp23 complex to enhance the pushing forces of branched actin networks
Actin filament severing
What are the details of F-actin actin severing via Cofilin?
- What binding sites play a role in the interaction?
- What’s the dynamics and thermodynamics of this interaction?
Sustained motility requires rapid filament turnover and subunit recycling. The essential regulatory protein cofilin accelerates network remodeling by severing actin filaments and increasing the concentration of ends available for elongation and subunit exchange.
Actin structures and their control in cells
The co-existence of multiple actin structures when they share the same pool of limited monomer supply is a topic of active research
Particularly, the size control of theses structures is of great importance (at least to me).
Relevant publications: Size control of multiple actin structures that use a shared supply of actin monomers
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@wossnerTheoryCoexistenceSelection2025
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@banerjeeSizeRegulationMultiple2022
- Need to read this one.
Also check:
Actin Isoforms, G-actin structure and polymerization animation in blender
Essays
These are some short essays as a part of this new learning method I am trying, where one writes essays about a topic to accelerate the recollection in the brain about said topic: