Filopodia (sg.: 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][further explanation needed] To close a wound in vertebrates, growth factors stimulate the formation of filopodia in fibroblasts to direct fibroblast migration and wound closure.[7] In macrophages, filopodia act as phagocytic tentacles, pulling bound objects towards the cell for phagocytosis.[8]
In infectionsedit
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.[9] Filopodia are the initial contact that human retinal pigment epithelial (RPE) cells make with elementary bodies of Chlamydia trachomatis, the bacteria that causes Chlamydia.[10]
Viruses have been shown to be transported along filopodia toward the cell body, leading to cell infection.[11] Directed transport of receptor-bound epidermal growth factor (EGF) along filopodia has also been described, supporting the proposed sensing function of filopodia.[12]
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.[14][15]
^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.
^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. PMC3218608. PMID 21975550.
^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. PMC2139807. PMID 9334343.
^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.
^ abOhta 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. PMC26747. PMID 10051605.
^ abBentley 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.
^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. PMC1913848. PMID 17620618.
^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. PMC5955597. PMID 29727463.
^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. PMC2171413. PMID 16027225.
^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. PMC2171515. PMID 16103229.
^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. PMC7321036. PMID 32645325.
^Beardsley J (June 1999). "Getting Wired". Scientific American. 280 (6): 24. Bibcode:1999SciAm.280f..24B. doi:10.1038/scientificamerican0699-24b (inactive 2024-02-22).{{cite journal}}: CS1 maint: DOI inactive as of February 2024 (link)
^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.
^Lloreda, Claudia López (16 December 2022). "Adult mouse brains are teeming with 'silent synapses'". Retrieved 18 December 2022.
^Vardalaki, Dimitra; Chung, Kwanghun; Harnett, Mark T. (December 2022). "Filopodia are a structural substrate for silent synapses in adult neocortex". Nature. 612 (7939): 323–327. Bibcode:2022Natur.612..323V. doi:10.1038/s41586-022-05483-6. ISSN 1476-4687. PMID 36450984. S2CID 254122483.
University press release: Trafton, Anne. "Silent synapses are abundant in the adult brain". Massachusetts Institute of Technology via medicalxpress.com. Retrieved 18 December 2022.
External linksedit
MBInfo - Filopodia
MBInfo - Filopodia Assembly
New Form of Cinema: Cellular Film, proposal for documentaries with cellular imaging