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Filopodia

Filopodia (singular 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, 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.[7] 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.[7] Filopodia-like projections have also been linked to dendrite creation when new synapses are formed in the brain.[8][9] In macrophages, filopodia act as phagocytic tentacles, pulling bound objects towards the cell for phagocytosis.[10]

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.[11] Filopodia are the initial contact that human retinal pigment epithelial (RPE) cells make with elementary bodies of Chlamydia trachomatis, the bacteria that causes Chlamydia.[12]

Viruses have been shown to be transported along filopodia toward the cell body, leading to cell infection.[13] Directed transport of receptor-bound epidermal growth factor (EGF) along filopodia has also been described, supporting the proposed sensing function of filopodia.[14]

SARS-CoV-2, the strain of coronavirus responsible for coronavirus disease 2019, produces filopodia in infected cells.[15]

References

  1. ^ Jump up to:a b Mattila PK, Lappalainen P (June 2008). “Filopodia: molecular architecture and cellular functions”. Nature Reviews. Molecular Cell Biology. 9 (6): 446–454. doi:10.1038/nrm2406. PMID 18464790. S2CID 33533182.
  2. ^ Small JV, Stradal T, Vignal E, Rottner K (March 2002). “The lamellipodium: where motility begins”. Trends in Cell Biology. 12 (3): 112–120. doi:10.1016/S0962-8924(01)02237-1. PMID 11859023.
  3. ^ Khurana S, George SP (September 2011). “The role of actin bundling proteins in the assembly of filopodia in epithelial cells”. Cell Adhesion & Migration. 5 (5): 409–420. doi:10.4161/cam.5.5.17644. PMC 3218608. PMID 21975550.
  4. ^ Hanein D, Matsudaira P, DeRosier DJ (October 1997). “Evidence for a conformational change in actin induced by fimbrin (N375) binding”. The Journal of Cell Biology. 139 (2): 387–396. doi:10.1083/jcb.139.2.387. PMC 2139807. PMID 9334343.
  5. ^ Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J, eds. (2004). Molecular Cell Biology (fifth ed.). W.H. Freeman and Company. pp. 821, 823.
  6. ^ Jump up to:a b Ohta Y, Suzuki N, Nakamura S, Hartwig JH, Stossel TP (March 1999). “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. Bibcode:1999PNAS…96.2122O. doi:10.1073/pnas.96.5.2122. PMC 26747. PMID 10051605.
  7. ^ Jump up to:a b Bentley D, Toroian-Raymond A (1986). “Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment”. Nature. 323 (6090): 712–715. Bibcode:1986Natur.323..712B. doi:10.1038/323712a0. PMID 3773996. S2CID 4371667.
  8. ^ Beardsley J (June 1999). “Getting Wired”. Scientific American. 280 (6): 24. Bibcode:1999SciAm.280f..24B. doi:10.1038/scientificamerican0699-24b.
  9. ^ Maletic-Savatic M, Malinow R, Svoboda K (March 1999). “Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity”. Science. 283 (5409): 1923–1927. doi:10.1126/science.283.5409.1923. PMID 10082466.
  10. ^ Kress H, Stelzer EH, Holzer D, Buss F, Griffiths G, Rohrbach A (July 2007). “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. Bibcode:2007PNAS..10411633K. doi:10.1073/pnas.0702449104. PMC 1913848. PMID 17620618.
  11. ^ Thomas S, Popov VL, Walker DH (December 2010). “Exit mechanisms of the intracellular bacterium Ehrlichia”. PLOS ONE. 5 (12): e15775. doi:10.1371/journal.pone.0015775. PMC 3004962. PMID 21187937.
  12. ^ Ford C, Nans A, Boucrot E, Hayward RD (May 2018). Welch MD (ed.). “Chlamydia exploits filopodial capture and a macropinocytosis-like pathway for host cell entry”. PLOS Pathogens. 14 (5): e1007051. doi:10.1371/journal.ppat.1007051. PMC 5955597. PMID 29727463.
  13. ^ Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W (July 2005). “Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells”. The Journal of Cell Biology. 170 (2): 317–325. doi:10.1083/jcb.200503059. PMC 2171413. PMID 16027225.
  14. ^ Lidke DS, Lidke KA, Rieger B, Jovin TM, Arndt-Jovin DJ (August 2005). “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. doi:10.1083/jcb.200503140. PMC 2171515. PMID 16103229.
  15. ^ Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, et al. (August 2020). “The Global Phosphorylation Landscape of SARS-CoV-2 Infection”. Cell. 182 (3): 685–712.e19. doi:10.1016/j.cell.2020.06.034. PMC 7321036. PMID 32645325.

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