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Filopodia

Actin projections on the leading edge of lamellipodia of migrating cells

Filopodia

Summary

Actin projections on the leading edge of lamellipodia of migrating cells

lamellipodial network]].

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

Filopodia have roles in sensing, migration, neurite outgrowth, and cell-cell interaction. 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.

Functions and variants

Many cell types have filopodia. The functions of filopodia have been attributed to pathfinding of neurons, early stages of synapse formation, antigen presentation by dendritic cells of the immune system, force generation by macrophages and virus transmission. They have been associated with wound closure, dorsal closure of Drosophila embryos, chemotaxis in Dictyostelium, Delta-Notch signaling, vasculogenesis, cell adhesion, cell migration, and cancer metastasis. Specific kinds of filopodia have been given various names: microspikes, pseudopods, thin filopodia, thick filopodia, gliopodia, myopodia, invadopodia, podosomes, telopodes, tunneling nanotubes 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. Filopodia are the initial contact that human retinal pigment epithelial (RPE) cells make with elementary bodies of Chlamydia trachomatis, the bacteria that causes chlamydia.

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

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

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

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.

  • University press release:

References

References

  1. (June 2008). "Filopodia: molecular architecture and cellular functions". Nature Reviews. Molecular Cell Biology.
  2. (March 2002). "The lamellipodium: where motility begins". Trends in Cell Biology.
  3. (September 2011). "The role of actin bundling proteins in the assembly of filopodia in epithelial cells". Cell Adhesion & Migration.
  4. (October 1997). "Evidence for a conformational change in actin induced by fimbrin (N375) binding". The Journal of Cell Biology.
  5. (2004). "Molecular Cell Biology". W.H. Freeman and Company.
  6. (March 1999). "The small GTPase RalA targets filamin to induce filopodia". Proceedings of the National Academy of Sciences of the United States of America.
  7. (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.
  8. (1986). "Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment". Nature.
  9. (January 2004). "Genesis of dendritic spines: insights from ultrastructural and imaging studies". Nature Reviews. Neuroscience.
  10. (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.
  11. (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.
  12. (July 2005). "Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells". The Journal of Cell Biology.
  13. (April 1986). "Epithelial wound closure in the rabbit cornea. A biphasic process". Investigative Ophthalmology & Visual Science.
  14. (November 2000). "Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure". Current Biology.
  15. (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.
  16. (July 2010). "Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition". Developmental Cell.
  17. (June 2023). "Coupling dynamics of 2D Notch-Delta signalling". Mathematical Biosciences.
  18. (August 2002). "In vivo imaging of embryonic vascular development using transgenic zebrafish". Developmental Biology.
  19. (January 2000). "Directed actin polymerization is the driving force for epithelial cell-cell adhesion". Cell.
  20. (August 1995). "Dynamics of thin filopodia during sea urchin gastrulation". Development.
  21. (December 1999). "The role of thin filopodia in motility and morphogenesis". Experimental Cell Research.
  22. (January 2006). "Gliopodia extend the range of direct glia-neuron communication during the CNS development in Drosophila". Molecular and Cellular Neurosciences.
  23. (October 2000). "Postsynaptic filopodia in muscle cells interact with innervating motoneuron axons". Nature Neuroscience.
  24. (August 1989). "Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells". The Journal of Experimental Zoology.
  25. (July 1985). "Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes". Experimental Cell Research.
  26. (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.
  27. (February 2004). "Nanotubular highways for intercellular organelle transport". Science.
  28. (December 2010). "Exit mechanisms of the intracellular bacterium Ehrlichia". PLOS ONE.
  29. (May 2018). "Chlamydia exploits filopodial capture and a macropinocytosis-like pathway for host cell entry". PLOS Pathogens.
  30. (July 2005). "Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells". The Journal of Cell Biology.
  31. (August 2005). "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors". The Journal of Cell Biology.
  32. (August 2020). "The Global Phosphorylation Landscape of SARS-CoV-2 Infection". Cell.
  33. (1986). "Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment". Nature.
  34. (June 1999). "Getting Wired". Scientific American.
  35. (March 1999). "Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity". Science.
  36. (16 December 2022). "Adult mouse brains are teeming with 'silent synapses'".
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