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]
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]
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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]
^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. PMID11859023.
^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.
^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. PMID14708001. S2CID15126232.
^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. PMID11478849.
^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. PMID10585250.
^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. PMID16298140. S2CID39541898.
^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. PMID11017174. S2CID23718828.
^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. PMID2549171.
^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. PMID2411576.