Filopodia
{{short description|Actin projections on the leading edge of lamellipodia of migrating cells}}
{{redirect|Microspikes|the hiking footgear|Crampons#Microspikes}}
Image:Filopodia.jpg which were born in and converged from the lamellipodial network.]]
Filopodia ({{singular}}: filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells.{{cite journal | vauthors = Mattila PK, Lappalainen P | title = Filopodia: molecular architecture and cellular functions | journal = Nature Reviews. Molecular Cell Biology | volume = 9 | issue = 6 | pages = 446–454 | date = June 2008 | pmid = 18464790 | doi = 10.1038/nrm2406 | s2cid = 33533182 | url = https://www.utupub.fi/handle/10024/159021 }} Within the lamellipodium, actin ribs are known as microspikes, and when they extend beyond the lamellipodia, they're known as filopodia.{{cite journal | vauthors = Small JV, Stradal T, Vignal E, Rottner K | title = The lamellipodium: where motility begins | journal = Trends in Cell Biology | volume = 12 | issue = 3 | pages = 112–120 | date = March 2002 | pmid = 11859023 | doi = 10.1016/S0962-8924(01)02237-1 }} They contain microfilaments (also called actin filaments) cross-linked into bundles by actin-bundling proteins,{{cite journal | vauthors = Khurana S, George SP | title = The role of actin bundling proteins in the assembly of filopodia in epithelial cells | journal = Cell Adhesion & Migration | volume = 5 | issue = 5 | pages = 409–420 | date = September 2011 | pmid = 21975550 | pmc = 3218608 | doi = 10.4161/cam.5.5.17644 }} such as fascin and fimbrin.{{cite journal | vauthors = Hanein D, Matsudaira P, DeRosier DJ | title = Evidence for a conformational change in actin induced by fimbrin (N375) binding | journal = The Journal of Cell Biology | volume = 139 | issue = 2 | pages = 387–396 | date = October 1997 | pmid = 9334343 | pmc = 2139807 | doi = 10.1083/jcb.139.2.387 }} Filopodia form focal adhesions with the substratum, linking them to the cell surface.{{cite book | title =Molecular Cell Biology | edition = fifth | veditors = Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J | pages = 821, 823 | date = 2004 | publisher = W.H. Freeman and Company }} Many types of migrating cells display filopodia, which are thought to be involved in both sensation of chemotropic cues, and resulting changes in directed locomotion.
Activation of the Rho family of GTPases, particularly Cdc42 and their downstream intermediates, results in the polymerization of actin fibers by Ena/Vasp homology proteins.{{cite journal | vauthors = Ohta Y, Suzuki N, Nakamura S, Hartwig JH, Stossel TP | title = The small GTPase RalA targets filamin to induce filopodia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 5 | pages = 2122–2128 | date = March 1999 | pmid = 10051605 | pmc = 26747 | doi = 10.1073/pnas.96.5.2122 | doi-access = free | bibcode = 1999PNAS...96.2122O }} Growth factors bind to receptor tyrosine kinases resulting in the polymerization of actin filaments, which, when cross-linked, make up the supporting cytoskeletal elements of filopodia. Rho activity also results in activation by phosphorylation of ezrin-moesin-radixin family proteins that link actin filaments to the filopodia membrane.
Filopodia have roles in sensing, migration, neurite outgrowth, and cell-cell interaction.{{elucidate|date=February 2023}} To close a wound in vertebrates, growth factors stimulate the formation of filopodia in fibroblasts to direct fibroblast migration and wound closure. In macrophages, filopodia act as phagocytic tentacles, pulling bound objects towards the cell for phagocytosis.{{cite journal | vauthors = Kress H, Stelzer EH, Holzer D, Buss F, Griffiths G, Rohrbach A | title = Filopodia act as phagocytic tentacles and pull with discrete steps and a load-dependent velocity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 28 | pages = 11633–11638 | date = July 2007 | pmid = 17620618 | pmc = 1913848 | doi = 10.1073/pnas.0702449104 | doi-access = free | bibcode = 2007PNAS..10411633K }}
Functions and variants
Many cell types have filopodia.{{Citation needed|date=September 2024}} The functions of filopodia have been attributed to pathfinding of neurons,{{cite journal |vauthors=Bentley D, Toroian-Raymond A |year=1986 |title=Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment |journal=Nature |volume=323 |issue=6090 |pages=712–5 |bibcode=1986Natur.323..712B |doi=10.1038/323712a0 |pmid=3773996 |s2cid=4371667}} early stages of synapse formation,{{cite journal |vauthors=Yuste R, Bonhoeffer T |date=January 2004 |title=Genesis of dendritic spines: insights from ultrastructural and imaging studies |journal=Nature Reviews. Neuroscience |volume=5 |issue=1 |pages=24–34 |doi=10.1038/nrn1300 |pmid=14708001 |s2cid=15126232}} antigen presentation by dendritic cells of the immune system,{{cite journal |vauthors=Raghunathan A, Sivakamasundari R, Wolenski J, Poddar R, Weissman SM |date=August 2001 |title=Functional analysis of B144/LST1: a gene in the tumor necrosis factor cluster that induces formation of long filopodia in eukaryotic cells |journal=Experimental Cell Research |volume=268 |issue=2 |pages=230–44 |doi=10.1006/excr.2001.5290 |pmid=11478849}} force generation by macrophages{{cite journal |vauthors=Kress H, Stelzer EH, Holzer D, Buss F, Griffiths G, Rohrbach A |date=July 2007 |title=Filopodia act as phagocytic tentacles and pull with discrete steps and a load-dependent velocity |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=104 |issue=28 |pages=11633–8 |bibcode=2007PNAS..10411633K |doi=10.1073/pnas.0702449104 |pmc=1913848 |pmid=17620618 |doi-access=free}} and virus transmission.{{cite journal |vauthors=Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W |date=July 2005 |title=Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells |journal=The Journal of Cell Biology |volume=170 |issue=2 |pages=317–25 |doi=10.1083/jcb.200503059 |pmc=2171413 |pmid=16027225}} They have been associated with wound closure,{{cite journal |vauthors=Crosson CE, Klyce SD, Beuerman RW |date=April 1986 |title=Epithelial wound closure in the rabbit cornea. A biphasic process |url=http://iovs.arvojournals.org/article.aspx?volume=27&page=464 |journal=Investigative Ophthalmology & Visual Science |volume=27 |issue=4 |pages=464–73 |pmid=3957565}} dorsal closure of Drosophila embryos,{{cite journal |vauthors=Jacinto A, Wood W, Balayo T, Turmaine M, Martinez-Arias A, Martin P |date=November 2000 |title=Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure |journal=Current Biology |volume=10 |issue=22 |pages=1420–6 |doi=10.1016/S0960-9822(00)00796-X |pmid=11102803 |doi-access=free|bibcode=2000CBio...10.1420J }} chemotaxis in Dictyostelium,{{cite journal |vauthors=Han YH, Chung CY, Wessels D, Stephens S, Titus MA, Soll DR, Firtel RA |date=December 2002 |title=Requirement of a vasodilator-stimulated phosphoprotein family member for cell adhesion, the formation of filopodia, and chemotaxis in dictyostelium |journal=The Journal of Biological Chemistry |volume=277 |issue=51 |pages=49877–87 |doi=10.1074/jbc.M209107200 |pmid=12388544 |doi-access=free}} Delta-Notch signaling,{{cite journal |vauthors=Cohen M, Georgiou M, Stevenson NL, Miodownik M, Baum B |date=July 2010 |title=Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition |journal=Developmental Cell |volume=19 |issue=1 |pages=78–89 |doi=10.1016/j.devcel.2010.06.006 |pmid=20643352 |doi-access=free}}{{cite journal |vauthors=Berkemeier F, Page, KM |date=June 2023 |title=Coupling dynamics of 2D Notch-Delta signalling |journal=Mathematical Biosciences |volume=360 |issue=1 |doi=10.1016/j.mbs.2023.109012 |pmid=37142213 |doi-access=free}} vasculogenesis,{{cite journal |vauthors=Lawson ND, Weinstein BM |date=August 2002 |title=In vivo imaging of embryonic vascular development using transgenic zebrafish |journal=Developmental Biology |volume=248 |issue=2 |pages=307–18 |doi=10.1006/dbio.2002.0711 |pmid=12167406 |doi-access=free}} cell adhesion,{{cite journal |vauthors=Vasioukhin V, Bauer C, Yin M, Fuchs E |date=January 2000 |title=Directed actin polymerization is the driving force for epithelial cell-cell adhesion |journal=Cell |volume=100 |issue=2 |pages=209–19 |doi=10.1016/S0092-8674(00)81559-7 |pmid=10660044 |doi-access=free}} cell migration, and cancer metastasis. Specific kinds of filopodia have been given various names:{{Citation needed|date=September 2024}} microspikes, pseudopods, thin filopodia,{{cite journal |vauthors=Miller J, Fraser SE, McClay D |date=August 1995 |title=Dynamics of thin filopodia during sea urchin gastrulation |url=http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=7671814 |journal=Development |volume=121 |issue=8 |pages=2501–11 |doi=10.1242/dev.121.8.2501 |pmid=7671814}} thick filopodia,{{cite journal |vauthors=McClay DR |date=December 1999 |title=The role of thin filopodia in motility and morphogenesis |journal=Experimental Cell Research |volume=253 |issue=2 |pages=296–301 |doi=10.1006/excr.1999.4723 |pmid=10585250}} gliopodia,{{cite journal |vauthors=Vasenkova I, Luginbuhl D, Chiba A |date=January 2006 |title=Gliopodia extend the range of direct glia-neuron communication during the CNS development in Drosophila |journal=Molecular and Cellular Neurosciences |volume=31 |issue=1 |pages=123–30 |doi=10.1016/j.mcn.2005.10.001 |pmid=16298140 |s2cid=39541898}} myopodia,{{cite journal |vauthors=Ritzenthaler S, Suzuki E, Chiba A |date=October 2000 |title=Postsynaptic filopodia in muscle cells interact with innervating motoneuron axons |journal=Nature Neuroscience |volume=3 |issue=10 |pages=1012–7 |doi=10.1038/79833 |pmid=11017174 |s2cid=23718828}} invadopodia,{{cite journal |vauthors=Chen WT |date=August 1989 |title=Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells |journal=The Journal of Experimental Zoology |volume=251 |issue=2 |pages=167–85 |doi=10.1002/jez.1402510206 |pmid=2549171}} podosomes,{{cite journal |vauthors=Tarone G, Cirillo D, Giancotti FG, Comoglio PM, Marchisio PC |date=July 1985 |title=Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes |journal=Experimental Cell Research |volume=159 |issue=1 |pages=141–57 |doi=10.1016/S0014-4827(85)80044-6 |pmid=2411576}} telopodes,{{cite journal |vauthors=Popescu LM, Faussone-Pellegrini MS |date=April 2010 |title=TELOCYTES - a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES |journal=Journal of Cellular and Molecular Medicine |volume=14 |issue=4 |pages=729–40 |doi=10.1111/j.1582-4934.2010.01059.x |pmc=3823108 |pmid=20367664}} tunneling nanotubes{{cite journal |vauthors=Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH |date=February 2004 |title=Nanotubular highways for intercellular organelle transport |journal=Science |volume=303 |issue=5660 |pages=1007–10 |bibcode=2004Sci...303.1007R |doi=10.1126/science.1093133 |pmid=14963329 |s2cid=37863055}} and dendrites.
In infections
Filopodia are also used for movement of bacteria between cells, so as to evade the host immune system. The intracellular bacteria Ehrlichia are transported between cells through the host cell filopodia induced by the pathogen during initial stages of infection.{{cite journal | vauthors = Thomas S, Popov VL, Walker DH | title = Exit mechanisms of the intracellular bacterium Ehrlichia | journal = PLOS ONE | volume = 5 | issue = 12 | pages = e15775 | date = December 2010 | pmid = 21187937 | pmc = 3004962 | doi = 10.1371/journal.pone.0015775 | bibcode = 2010PLoSO...515775T | doi-access = free }} Filopodia are the initial contact that human retinal pigment epithelial (RPE) cells make with elementary bodies of Chlamydia trachomatis, the bacteria that causes chlamydia.{{cite journal | vauthors = Ford C, Nans A, Boucrot E, Hayward RD | title = Chlamydia exploits filopodial capture and a macropinocytosis-like pathway for host cell entry | journal = PLOS Pathogens | volume = 14 | issue = 5 | pages = e1007051 | date = May 2018 | pmid = 29727463 | pmc = 5955597 | doi = 10.1371/journal.ppat.1007051 | veditors = Welch MD | doi-access = free }}
Viruses have been shown to be transported along filopodia toward the cell body, leading to cell infection.{{cite journal | vauthors = Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W | title = Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells | journal = The Journal of Cell Biology | volume = 170 | issue = 2 | pages = 317–325 | date = July 2005 | pmid = 16027225 | pmc = 2171413 | doi = 10.1083/jcb.200503059 }} Directed transport of receptor-bound epidermal growth factor (EGF) along filopodia has also been described, supporting the proposed sensing function of filopodia.{{cite journal | vauthors = Lidke DS, Lidke KA, Rieger B, Jovin TM, Arndt-Jovin DJ | title = Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors | journal = The Journal of Cell Biology | volume = 170 | issue = 4 | pages = 619–626 | date = August 2005 | pmid = 16103229 | pmc = 2171515 | doi = 10.1083/jcb.200503140 }}
SARS-CoV-2, the strain of coronavirus responsible for COVID-19, produces filopodia in infected cells.{{cite journal | vauthors = Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray M, Miorin L, Moreno E, Koh C, Tran QD, Hardy A, Robinot R, Vallet T, Nilsson-Payant BE, Hernandez-Armenta C, Dunham A, Weigang S, Knerr J, Modak M, Quintero D, Zhou Y, Dugourd A, Valdeolivas A, Patil T, Li Q, Hüttenhain R, Cakir M, Muralidharan M, Kim M, Jang G, Tutuncuoglu B, Hiatt J, Guo JZ, Xu J, Bouhaddou S, Mathy CJ, Gaulton A, Manners EJ, Félix E, Shi Y, Goff M, Lim JK, McBride T, O'Neal MC, Cai Y, Chang JC, Broadhurst DJ, Klippsten S, De Wit E, Leach AR, Kortemme T, Shoichet B, Ott M, Saez-Rodriguez J, tenOever BR, Mullins RD, Fischer ER, Kochs G, Grosse R, García-Sastre A, Vignuzzi M, Johnson JR, Shokat KM, Swaney DL, Beltrao P, Krogan NJ | display-authors = 6 | title = The Global Phosphorylation Landscape of SARS-CoV-2 Infection | journal = Cell | volume = 182 | issue = 3 | pages = 685–712.e19 | date = August 2020 | pmid = 32645325 | pmc = 7321036 | doi = 10.1016/j.cell.2020.06.034 | doi-access = free }}
In brain cells
{{Expand section|date=February 2023}}
In developing neurons, filopodia extend from the growth cone at the leading edge. In neurons deprived of filopodia by partial inhibition of actin filaments polymerization, growth cone extension continues as normal, but direction of growth is disrupted and highly irregular.{{cite journal | vauthors = Bentley D, Toroian-Raymond A | title = Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment | journal = Nature | volume = 323 | issue = 6090 | pages = 712–715 | year = 1986 | pmid = 3773996 | doi = 10.1038/323712a0 | s2cid = 4371667 | bibcode = 1986Natur.323..712B }} Filopodia-like projections have also been linked to dendrite creation when new synapses are formed in the brain.{{cite journal| vauthors = Beardsley J |title=Getting Wired|journal=Scientific American|date=June 1999|volume=280 |issue=6 |page=24 |doi=10.1038/scientificamerican0699-24b |doi-broken-date=1 November 2024 |bibcode=1999SciAm.280f..24B }}{{cite journal | vauthors = Maletic-Savatic M, Malinow R, Svoboda K | title = Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity | journal = Science | volume = 283 | issue = 5409 | pages = 1923–1927 | date = March 1999 | pmid = 10082466 | doi = 10.1126/science.283.5409.1923 | author3-link = Karel Svoboda (scientist) }}
A study deploying protein imaging of adult mice showed that filopodia in the explored regions were by an order of magnitude more abundant than previously believed, comprising about 30% of all dendritic protrusions. At their tips, they contain "silent synapses" that are inactive until recruited as part of neural plasticity and flexible learning or memories, previously thought to be present mainly in the developing pre-adult brain and to die off with time.{{cite news |last1=Lloreda |first1=Claudia López |title=Adult mouse brains are teeming with 'silent synapses' |url=https://www.sciencenews.org/article/adult-mouse-brains-silent-synapses-memories |access-date=18 December 2022 |date=16 December 2022}}{{cite journal |last1=Vardalaki |first1=Dimitra |last2=Chung |first2=Kwanghun |last3=Harnett |first3=Mark T. |title=Filopodia are a structural substrate for silent synapses in adult neocortex |journal=Nature |date=December 2022 |volume=612 |issue=7939 |pages=323–327 |doi=10.1038/s41586-022-05483-6 |pmid=36450984 |bibcode=2022Natur.612..323V |s2cid=254122483 |url=https://www.nature.com/articles/s41586-022-05483-6 |language=en |issn=1476-4687|url-access=subscription}}
- University press release: {{cite news |last1=Trafton |first1=Anne |title=Silent synapses are abundant in the adult brain |url=https://medicalxpress.com/news/2022-11-silent-synapses-abundant-adult-brain.html |access-date=18 December 2022 |work=Massachusetts Institute of Technology via medicalxpress.com |language=en}}{{elucidate|date=February 2023}}
References
{{Reflist}}
External links
- [http://www.mechanobio.info/topics/cytoskeleton-dynamics/go-0030175 MBInfo - Filopodia]
- [http://www.mechanobio.info/topics/cytoskeleton-dynamics/go-0030175/go-0046847 MBInfo - Filopodia Assembly]
- [https://myredhotphilosophy.blogspot.com/2011/03/new-form-of-cinema-cellular-film.html New Form of Cinema: Cellular Film], proposal for documentaries with cellular imaging
{{Authority control}}