Filopodia

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This electron micrograph shows exaggerated filopodia with club-like shape induced by formin mDia2 in cultured cells. These filopodia are filled with bundled actin filaments which were born in and converged from the lamellipodial network. Filopodia.jpg
This electron micrograph shows exaggerated filopodia with club-like shape induced by formin mDia2 in cultured cells. These filopodia are filled with bundled actin filaments which were born in and converged from the lamellipodial network.

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.

Contents

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]

Functions and variants

Many cell types have filopodia.[ citation needed ] The functions of filopodia have been attributed to pathfinding of neurons, [9] early stages of synapse formation, [10] antigen presentation by dendritic cells of the immune system, [11] force generation by macrophages [12] and virus transmission. [13] They have been associated with wound closure, [14] dorsal closure of Drosophila embryos, [15] chemotaxis in Dictyostelium, [16] Delta-Notch signaling, [17] [18] vasculogenesis, [19] cell adhesion, [20] cell migration, and cancer metastasis. Specific kinds of filopodia have been given various names:[ citation needed ] microspikes, pseudopods, thin filopodia, [21] thick filopodia, [22] gliopodia, [23] myopodia, [24] invadopodia, [25] podosomes, [26] telopodes, [27] tunneling nanotubes [28] 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. [29] Filopodia are the initial contact that human retinal pigment epithelial (RPE) cells make with elementary bodies of Chlamydia trachomatis , the bacteria that causes chlamydia. [30]

Viruses have been shown to be transported along filopodia toward the cell body, leading to cell infection. [31] Directed transport of receptor-bound epidermal growth factor (EGF) along filopodia has also been described, supporting the proposed sensing function of filopodia. [32]

SARS-CoV-2, the strain of coronavirus responsible for COVID-19, produces filopodia in infected cells. [33]

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. [7] Filopodia-like projections have also been linked to dendrite creation when new synapses are formed in the brain. [34] [35]

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. [36] [37] [ further explanation needed ]

References

  1. 1 2 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. 1 2 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. 1 2 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. ↑ 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.
  9. ↑ Bentley D, Toroian-Raymond A (1986). "Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment". Nature. 323 (6090): 712–5. Bibcode:1986Natur.323..712B. doi:10.1038/323712a0. PMID   3773996. S2CID   4371667.
  10. ↑ Yuste R, Bonhoeffer T (January 2004). "Genesis of dendritic spines: insights from ultrastructural and imaging studies". Nature Reviews. Neuroscience. 5 (1): 24–34. doi:10.1038/nrn1300. PMID   14708001. S2CID   15126232.
  11. ↑ Raghunathan A, Sivakamasundari R, Wolenski J, Poddar R, Weissman SM (August 2001). "Functional analysis of B144/LST1: a gene in the tumor necrosis factor cluster that induces formation of long filopodia in eukaryotic cells". Experimental Cell Research. 268 (2): 230–44. doi:10.1006/excr.2001.5290. PMID   11478849.
  12. ↑ 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): 11633–8. Bibcode:2007PNAS..10411633K. doi: 10.1073/pnas.0702449104 . PMC   1913848 . PMID   17620618.
  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): 317–25. doi:10.1083/jcb.200503059. PMC   2171413 . PMID   16027225.
  14. ↑ Crosson CE, Klyce SD, Beuerman RW (April 1986). "Epithelial wound closure in the rabbit cornea. A biphasic process". Investigative Ophthalmology & Visual Science. 27 (4): 464–73. PMID   3957565.
  15. ↑ Jacinto A, Wood W, Balayo T, Turmaine M, Martinez-Arias A, Martin P (November 2000). "Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure". Current Biology. 10 (22): 1420–6. Bibcode:2000CBio...10.1420J. doi: 10.1016/S0960-9822(00)00796-X . PMID   11102803.
  16. ↑ Han YH, Chung CY, Wessels D, Stephens S, Titus MA, Soll DR, Firtel RA (December 2002). "Requirement of a vasodilator-stimulated phosphoprotein family member for cell adhesion, the formation of filopodia, and chemotaxis in dictyostelium". The Journal of Biological Chemistry. 277 (51): 49877–87. doi: 10.1074/jbc.M209107200 . PMID   12388544.
  17. ↑ Cohen M, Georgiou M, Stevenson NL, Miodownik M, Baum B (July 2010). "Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition". Developmental Cell. 19 (1): 78–89. doi: 10.1016/j.devcel.2010.06.006 . PMID   20643352.
  18. ↑ Berkemeier F, Page, KM (June 2023). "Coupling dynamics of 2D Notch-Delta signalling". Mathematical Biosciences. 360 (1). doi: 10.1016/j.mbs.2023.109012 . PMID   37142213.
  19. ↑ Lawson ND, Weinstein BM (August 2002). "In vivo imaging of embryonic vascular development using transgenic zebrafish". Developmental Biology. 248 (2): 307–18. doi: 10.1006/dbio.2002.0711 . PMID   12167406.
  20. ↑ Vasioukhin V, Bauer C, Yin M, Fuchs E (January 2000). "Directed actin polymerization is the driving force for epithelial cell-cell adhesion". Cell. 100 (2): 209–19. doi: 10.1016/S0092-8674(00)81559-7 . PMID   10660044.
  21. ↑ Miller J, Fraser SE, McClay D (August 1995). "Dynamics of thin filopodia during sea urchin gastrulation" . Development. 121 (8): 2501–11. doi:10.1242/dev.121.8.2501. PMID   7671814.
  22. ↑ McClay DR (December 1999). "The role of thin filopodia in motility and morphogenesis". Experimental Cell Research. 253 (2): 296–301. doi:10.1006/excr.1999.4723. PMID   10585250.
  23. ↑ Vasenkova I, Luginbuhl D, Chiba A (January 2006). "Gliopodia extend the range of direct glia-neuron communication during the CNS development in Drosophila". Molecular and Cellular Neurosciences. 31 (1): 123–30. doi:10.1016/j.mcn.2005.10.001. PMID   16298140. S2CID   39541898.
  24. ↑ Ritzenthaler S, Suzuki E, Chiba A (October 2000). "Postsynaptic filopodia in muscle cells interact with innervating motoneuron axons". Nature Neuroscience. 3 (10): 1012–7. doi:10.1038/79833. PMID   11017174. S2CID   23718828.
  25. ↑ Chen WT (August 1989). "Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells". The Journal of Experimental Zoology. 251 (2): 167–85. doi:10.1002/jez.1402510206. PMID   2549171.
  26. ↑ Tarone G, Cirillo D, Giancotti FG, Comoglio PM, Marchisio PC (July 1985). "Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes". Experimental Cell Research. 159 (1): 141–57. doi:10.1016/S0014-4827(85)80044-6. PMID   2411576.
  27. ↑ Popescu LM, Faussone-Pellegrini MS (April 2010). "TELOCYTES - a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES". Journal of Cellular and Molecular Medicine. 14 (4): 729–40. doi:10.1111/j.1582-4934.2010.01059.x. PMC   3823108 . PMID   20367664.
  28. ↑ Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH (February 2004). "Nanotubular highways for intercellular organelle transport". Science. 303 (5660): 1007–10. Bibcode:2004Sci...303.1007R. doi:10.1126/science.1093133. PMID   14963329. S2CID   37863055.
  29. ↑ Thomas S, Popov VL, Walker DH (December 2010). "Exit mechanisms of the intracellular bacterium Ehrlichia". PLOS ONE. 5 (12): e15775. Bibcode:2010PLoSO...515775T. doi: 10.1371/journal.pone.0015775 . PMC   3004962 . PMID   21187937.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ 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.
  34. ↑ Beardsley J (June 1999). "Getting Wired". Scientific American. 280 (6): 24. Bibcode:1999SciAm.280f..24B. doi:10.1038/scientificamerican0699-24b (inactive 1 November 2024).{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  35. ↑ 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.
  36. ↑ Lloreda, Claudia López (16 December 2022). "Adult mouse brains are teeming with 'silent synapses'" . Retrieved 18 December 2022.
  37. ↑ 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.
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