Filopodia Explained

Filopodia (: filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells.[1] Within the lamellipodium, actin ribs are known as microspikes, and when they extend beyond the lamellipodia, they're known as filopodia.[2] They contain microfilaments (also called actin filaments) cross-linked into bundles by actin-bundling proteins,[3] such as fascin and fimbrin.[4] Filopodia form focal adhesions with the substratum, linking them to the cell surface.[5] 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.[6] 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.[6]

Filopodia have roles in sensing, migration, neurite outgrowth, and cell-cell interaction.[1] 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.[7]

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.[8] Filopodia are the initial contact that human retinal pigment epithelial (RPE) cells make with elementary bodies of Chlamydia trachomatis, the bacteria that causes Chlamydia.[9]

Viruses have been shown to be transported along filopodia toward the cell body, leading to cell infection.[10] Directed transport of receptor-bound epidermal growth factor (EGF) along filopodia has also been described, supporting the proposed sensing function of filopodia.[11]

SARS-CoV-2, the strain of coronavirus responsible for COVID-19, produces filopodia in infected cells.[12]

In brain cells

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.[13] Filopodia-like projections have also been linked to dendrite creation when new synapses are formed in the brain.[14] [15]

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.[16] [17]

External links

Notes and References

  1. Mattila PK, Lappalainen P . Filopodia: molecular architecture and cellular functions . Nature Reviews. Molecular Cell Biology . 9 . 6 . 446–454 . June 2008 . 18464790 . 10.1038/nrm2406 . 33533182 .
  2. Small JV, Stradal T, Vignal E, Rottner K . The lamellipodium: where motility begins . Trends in Cell Biology . 12 . 3 . 112–120 . March 2002 . 11859023 . 10.1016/S0962-8924(01)02237-1 .
  3. Khurana S, George SP . The role of actin bundling proteins in the assembly of filopodia in epithelial cells . Cell Adhesion & Migration . 5 . 5 . 409–420 . September 2011 . 21975550 . 3218608 . 10.4161/cam.5.5.17644 .
  4. Hanein D, Matsudaira P, DeRosier DJ . Evidence for a conformational change in actin induced by fimbrin (N375) binding . The Journal of Cell Biology . 139 . 2 . 387–396 . October 1997 . 9334343 . 2139807 . 10.1083/jcb.139.2.387 .
  5. Book: Molecular Cell Biology . fifth . Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J . 821, 823 . 2004 . W.H. Freeman and Company .
  6. Ohta Y, Suzuki N, Nakamura S, Hartwig JH, Stossel TP . The small GTPase RalA targets filamin to induce filopodia . Proceedings of the National Academy of Sciences of the United States of America . 96 . 5 . 2122–2128 . March 1999 . 10051605 . 26747 . 10.1073/pnas.96.5.2122 . free . 1999PNAS...96.2122O .
  7. Kress H, Stelzer EH, Holzer D, Buss F, Griffiths G, Rohrbach A . Filopodia act as phagocytic tentacles and pull with discrete steps and a load-dependent velocity . Proceedings of the National Academy of Sciences of the United States of America . 104 . 28 . 11633–11638 . July 2007 . 17620618 . 1913848 . 10.1073/pnas.0702449104 . free . 2007PNAS..10411633K .
  8. Thomas S, Popov VL, Walker DH . Exit mechanisms of the intracellular bacterium Ehrlichia . PLOS ONE . 5 . 12 . e15775 . December 2010 . 21187937 . 3004962 . 10.1371/journal.pone.0015775 . 2010PLoSO...515775T . free .
  9. Ford C, Nans A, Boucrot E, Hayward RD . Chlamydia exploits filopodial capture and a macropinocytosis-like pathway for host cell entry . PLOS Pathogens . 14 . 5 . e1007051 . May 2018 . 29727463 . 5955597 . 10.1371/journal.ppat.1007051 . Welch MD . free .
  10. Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W . Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells . The Journal of Cell Biology . 170 . 2 . 317–325 . July 2005 . 16027225 . 2171413 . 10.1083/jcb.200503059 .
  11. Lidke DS, Lidke KA, Rieger B, Jovin TM, Arndt-Jovin DJ . Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors . The Journal of Cell Biology . 170 . 4 . 619–626 . August 2005 . 16103229 . 2171515 . 10.1083/jcb.200503140 .
  12. 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 . 6 . The Global Phosphorylation Landscape of SARS-CoV-2 Infection . Cell . 182 . 3 . 685–712.e19 . August 2020 . 32645325 . 7321036 . 10.1016/j.cell.2020.06.034 . free .
  13. Bentley D, Toroian-Raymond A . Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment . Nature . 323 . 6090 . 712–715 . 1986 . 3773996 . 10.1038/323712a0 . 4371667 . 1986Natur.323..712B .
  14. Beardsley J . Getting Wired. Scientific American. June 1999. 280 . 6 . 24 . 10.1038/scientificamerican0699-24b . 2024-02-22 . 1999SciAm.280f..24B .
  15. Maletic-Savatic M, Malinow R, Svoboda K . Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity . Science . 283 . 5409 . 1923–1927 . March 1999 . 10082466 . 10.1126/science.283.5409.1923 . Karel Svoboda (scientist) .
  16. News: Lloreda . Claudia López . Adult mouse brains are teeming with 'silent synapses' . 18 December 2022 . 16 December 2022.
  17. Vardalaki . Dimitra . Chung . Kwanghun . Harnett . Mark T. . Filopodia are a structural substrate for silent synapses in adult neocortex . Nature . December 2022 . 612 . 7939 . 323–327 . 10.1038/s41586-022-05483-6 . 36450984 . 2022Natur.612..323V . 254122483 . en . 1476-4687. subscription.

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