Editing Microfilament (section)

==Actin in cells==
Intracellular actin cytoskeletal assembly and disassembly are tightly regulated by cell signaling mechanisms. Many [[signal transduction]] systems use the actin cytoskeleton as a scaffold, holding them at or near the inner face of the peripheral [[lipid bilayer|membrane]]. This subcellular location allows immediate responsiveness to transmembrane receptor action and the resulting cascade of signal-processing enzymes.{{cn|date=June 2024}}

Because actin monomers must be recycled to sustain high rates of actin-based motility during [[chemotaxis]], cell signalling is believed to activate cofilin, the actin-filament depolymerizing protein which binds to ADP-rich actin subunits nearest the filament's pointed-end and promotes filament fragmentation, with concomitant depolymerization in order to liberate actin monomers. In most animal cells, monomeric actin is bound to [[profilin]] and [[thymosin beta-4]], both of which preferentially bind with one-to-one stoichiometry to ATP-containing monomers. Although thymosin beta-4 is strictly a monomer-sequestering protein, the behavior of profilin is far more complex. Profilin enhances the ability of monomers to assemble by stimulating the exchange of actin-bound ADP for solution-phase ATP to yield actin-ATP and ADP. Profilin is transferred to the leading edge by virtue of its [[Phosphatidylinositols|PIP<sub>2</sub>]] binding site, and it employs its poly-L-proline binding site to dock onto end-tracking proteins. Once bound, profilin-actin-ATP is loaded into the monomer-insertion site of actoclampin motors.{{cn|date=January 2023}}

Another important component in filament formation is the [[Arp2/3 complex]], which binds to the side of an already existing filament (or "mother filament"), where it nucleates the formation of a new daughter filament at a 70-degree angle relative to the mother filament, effecting a fan-like branched filament network.<ref>{{Cite journal |vauthors=Mullins RD, Heuser JA, Pollard TD |date=May 1998 |title=The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=95 |issue=11 |pages=6181–6 |bibcode=1998PNAS...95.6181M |doi=10.1073/pnas.95.11.6181 |pmc=27619 |pmid=9600938 |doi-access=free}}</ref>

Specialized unique actin cytoskeletal structures are found adjacent to the plasma membrane. Four remarkable examples include [[red blood cell]]s, [[HEK 293 cells|human embryonic kidney cells]], [[neuron]]s, and [[sperm]] cells. In red blood cells, a [[spectrin]]-actin [[hexagonal lattice]] is formed by interconnected short actin filaments.<ref>{{Cite journal |last=Gokhin |first=David S. |last2=Fowler |first2=Velia M. |author-link2=Velia Fowler |date=May 2016 |title=Feisty filaments: actin dynamics in the red blood cell membrane skeleton |journal=Current Opinion in Hematology |volume=23 |issue=3 |pages=206–214 |doi=10.1097/MOH.0000000000000227 |issn=1065-6251 |pmc=4966542 |pmid=27055045}}</ref> In human embryonic kidney cells, the cortical actin forms a scale-free [[fractal]] structure.<ref>{{Cite journal |last=Sadegh |first=Sanaz |last2=Higgins |first2=Jenny L. |last3=Mannion |first3=Patrick C. |last4=Tamkun |first4=Michael M. |last5=Krapf |first5=Diego |date=2017-03-09 |title=Plasma Membrane is Compartmentalized by a Self-Similar Cortical Actin Meshwork |journal=Physical Review X |volume=7 |issue=1 |pages=011031 |arxiv=1702.03997 |bibcode=2017PhRvX...7a1031S |doi=10.1103/PhysRevX.7.011031 |issn=2160-3308 |pmc=5500227 |pmid=28690919}}</ref> First found in neuronal [[axon]]s, actin forms periodic rings that are stabilized by spectrin and adducin<ref>{{Cite journal |last=Xu |first=K. |last2=Zhong |first2=G. |last3=Zhuang |first3=X. |date=2013-01-25 |title=Actin, Spectrin, and Associated Proteins Form a Periodic Cytoskeletal Structure in Axons |journal=Science |volume=339 |issue=6118 |pages=452–456 |bibcode=2013Sci...339..452X |doi=10.1126/science.1232251 |issn=0036-8075 |pmc=3815867 |pmid=23239625}}</ref><ref>{{Cite journal |last=D'Este |first=Elisa |last2=Kamin |first2=Dirk |last3=Göttfert |first3=Fabian |last4=El-Hady |first4=Ahmed |last5=Hell |first5=Stefan W. |date=March 2015 |title=STED Nanoscopy Reveals the Ubiquity of Subcortical Cytoskeleton Periodicity in Living Neurons |journal=Cell Reports |volume=10 |issue=8 |pages=1246–1251 |doi=10.1016/j.celrep.2015.02.007 |pmid=25732815 |doi-access=free |hdl-access=free |hdl=11858/00-001M-0000-0025-05F3-D}}</ref> {{endash}} and this ring structure was then found by He et al 2016 to occur in almost every neuronal type and [[glia|glial cells]], across seemingly every animal taxon including ''[[Caenorhabditis elegans]]'', ''[[Drosophila melanogaster|Drosophila]]'', ''[[Gallus gallus]]'' and ''[[Mus musculus]]''.<ref name="Sahl-et-al-2017">{{Cite journal |last=Sahl |first=Steffen J. |last2=Hell |first2=Stefan W. |last3=Jakobs |first3=Stefan |date=2017-09-06 |title=Fluorescence nanoscopy in cell biology |journal=[[Nature Reviews Molecular Cell Biology]] |publisher=[[Nature Portfolio]] |volume=18 |issue=11 |pages=685–701 |doi=10.1038/nrm.2017.71 |issn=1471-0072 |pmid=28875992 |s2cid=20747438}}</ref> And in mammalian sperm, actin forms a [[Helix|helical structure]] in the midpiece, i.e., the first segment of the [[flagellum]].<ref>{{Cite journal |last=Gervasi |first=María G. |last2=Xu |first2=Xinran |last3=Carbajal-Gonzalez |first3=Blanca |last4=Buffone |first4=Mariano G. |last5=Visconti |first5=Pablo E. |last6=Krapf |first6=Diego |date=2018-06-01 |title=The actin cytoskeleton of the mouse sperm flagellum is organized in a helical structure |journal=Journal of Cell Science |volume=131 |issue=11 |pages=jcs215897 |doi=10.1242/jcs.215897 |issn=0021-9533 |pmc=6031324 |pmid=29739876}}</ref>