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 ]

Related Research Articles

<span class="mw-page-title-main">Pseudopodia</span> False leg found on slime molds, archaea, protozoans, leukocytes and certain bacteria

A pseudopod or pseudopodium is a temporary arm-like projection of a eukaryotic cell membrane that is emerged in the direction of movement. Filled with cytoplasm, pseudopodia primarily consist of actin filaments and may also contain microtubules and intermediate filaments. Pseudopods are used for motility and ingestion. They are often found in amoebas.

<span class="mw-page-title-main">Dendritic spine</span> Small protrusion on a dendrite that receives input from a single axon

A dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body. Most spines have a bulbous head, and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons. It has also been suggested that changes in the activity of neurons have a positive effect on spine morphology.

<span class="mw-page-title-main">Actin</span> Family of proteins

Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm.

<span class="mw-page-title-main">Cell adhesion</span> Process of cell attachment

Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.

<span class="mw-page-title-main">Fimbrin</span> Protein-coding gene in the species Homo sapiens

Fimbrin also known as is plastin 1 is a protein that in humans is encoded by the PLS1 gene. Fimbrin is an actin cross-linking protein important in the formation of filopodia.

<span class="mw-page-title-main">Podosome</span>

Podosomes are conical, actin-rich structures found on the outer surface of the plasma membrane of animal cells. Their size ranges from approximately 0.5 μm to 2.0 μm in diameter. While usually situated on the periphery of the cellular membrane, these unique structures display a polarized pattern of distribution in migrating cells, situating at the front border between the lamellipodium and lamellum. Their primary purpose is connected to cellular motility and invasion; therefore, they serve as both sites of attachment and degradation along the extracellular matrix. Many different specialized cells exhibit these dynamic structures such as invasive cancer cells, osteoclasts, vascular smooth muscle cells, endothelial cells, and certain immune cells like macrophages and dendritic cells.

<span class="mw-page-title-main">Adherens junction</span> Protein complexes at cell junctions

In cell biology, adherens junctions are protein complexes that occur at cell–cell junctions and cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell or as spots of attachment to the extracellular matrix.

In cell biology, contact inhibition refers to two different but closely related phenomena: contact inhibition of locomotion (CIL) and contact inhibition of proliferation (CIP). CIL refers to the avoidance behavior exhibited by fibroblast-like cells when in contact with one another. In most cases, when two cells contact each other, they attempt to alter their locomotion in a different direction to avoid future collision. When collision is unavoidable, a different phenomenon occurs whereby growth of the cells of the culture itself eventually stops in a cell-density dependent manner.

<span class="mw-page-title-main">Bleb (cell biology)</span> Bulge in the plasma membrane of a cell

In cell biology, a bleb is a bulge of the plasma membrane of a cell, characterized by a spherical, "blister-like", bulky morphology. It is characterized by the decoupling of the cytoskeleton from the plasma membrane, degrading the internal structure of the cell, allowing the flexibility required for the cell to separate into individual bulges or pockets of the intercellular matrix. Most commonly, blebs are seen in apoptosis, but they are also seen in other non-apoptotic functions, including apocrine secretion. Blebbing, or zeiosis, is the formation of blebs.

<span class="mw-page-title-main">Fascin</span> Actin bundling protein

Fascin is an actin bundling protein.

Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and α-actinin.

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog is a protein that in humans is encoded by the CDC42 gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">PTK2</span> Protein-coding gene in humans

PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.

<span class="mw-page-title-main">MYO10</span> Protein-coding gene in the species Homo sapiens

Myosin X, also known as MYO10, is a protein that in humans is encoded by the MYO10 gene.

<span class="mw-page-title-main">Stress fiber</span> Contractile actin bundles found in non-muscle cells

Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated actomyosin structure within non-muscle cells. Stress fibers have been shown to play an important role in cellular contractility, providing force for a number of functions such as cell adhesion, migration and morphogenesis.

Rif is a small signaling G protein, and is a member of the Rho family of GTPases. It is primarily active in the brain and plays a physiological role in the formation of neuronal dendritic spine. This process is regulated by FARP1, a type of activator for RhoA GTPases. Alternatively, Rif can induce the formation of actin stress fibers in epithelial cells, which is dependent on the activity levels of ROCK proteins since the absence of ROCK activity would mean Rif would be unable to stimulate the growth of stress fibers.

<span class="mw-page-title-main">Cadherin-1</span> Human protein-coding gene

Cadherin-1 or Epithelial cadherin(E-cadherin), is a protein that in humans is encoded by the CDH1 gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. CDH1 has also been designated as CD324. It is a tumor suppressor gene.

<span class="mw-page-title-main">MDia1</span> Protein

mDia1 is a member of the protein family called the formins and is a Rho effector. It is the mouse version of the diaphanous homolog 1 of Drosophila. mDia1 localizes to cells' mitotic spindle and midbody, plays a role in stress fiber and filopodia formation, phagocytosis, activation of serum response factor, formation of adherens junctions, and it can act as a transcription factor. mDia1 accelerates actin nucleation and elongation by interacting with barbed ends of actin filaments. The gene encoding mDia1 is located on Chromosome 18 of Mus musculus and named Diap1.

Paracytophagy is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells. The process of paracytophagy was first described as a crucial step during cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes, and is also commonly observed in Shigella flexneri. Paracytophagy allows these intracellular pathogens to spread directly from cell to cell, thus escaping immune detection and destruction. Studies of this process have contributed significantly to our understanding of the role of the actin cytoskeleton in eukaryotic cells.

<span class="mw-page-title-main">Synaptic stabilization</span> Modifying synaptic strength via cell adhesion molecules

Synaptic stabilization is crucial in the developing and adult nervous systems and is considered a result of the late phase of long-term potentiation (LTP). The mechanism involves strengthening and maintaining active synapses through increased expression of cytoskeletal and extracellular matrix elements and postsynaptic scaffold proteins, while pruning less active ones. For example, cell adhesion molecules (CAMs) play a large role in synaptic maintenance and stabilization. Gerald Edelman discovered CAMs and studied their function during development, which showed CAMs are required for cell migration and the formation of the entire nervous system. In the adult nervous system, CAMs play an integral role in synaptic plasticity relating to learning and memory.

References

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