Lamellipodia
Encyclopedia
The lamellipodium is a cytoskeletal
protein actin
projection on the mobile edge of the cell
. It contains a quasi-two-dimensional actin mesh; the whole structure propels the cell across a substrate (Alberts, et al., 2002). Within the lamellipodia are ribs of actin called microspikes, which, when they spread beyond the lamellipodium frontier, are called filopodia
(Small, et al., 2002). The lamellipodium is born of actin nucleation
in the plasma membrane of the cell (Alberts, et al., 2002) and is the primary area of actin incorporation or microfilament
formation of the cell.
Lamellipodia are found primarily in very mobile cells, for example the keratinocytes of fish
and frog
s, which are involved in the quick repair of wounds
, crawling at a speeds of 10-20μm/minute over epithelial
surfaces. A lamellipodium separated from the main part of a cell by scratching across the cell with a pipette
tip can continue to crawl freely about on its own.
Lamellipodia are a characteristic feature at the front, leading edge, of motile cells. They are believed to be the actual motor which pulls the cell forward during the process of cell migration
. The tip of the lamellipodium is the site where exocytosis
occurs in migrating mammalian cells as part of their clathrin
-mediated endocytic cycle
. This, together with actin-polymerisation there, helps extend the lamella forward and thus advance the cell's front. It thus acts as a steering device for cells in the process of chemotaxis
. It is also the site from which particles or aggregates attached to the cell surface migrate in a process known as cap formation
.
Structurally, the barbed ends of the microfilaments (localized actin monomer
s in an ATP
-bound form) face the "seeking" edge of the cell, while the pointed ends (localized actin monomers in an ADP
-bound form) face the lamella behind (Cramer, 1997). This creates treadmilling
throughout the lamellipodium, which aids in the retrograde flow of particles throughout (ibid.). Arp2/3 complex
es are present at microfilament-microfilament junctions in lamellipodia, and help create the actin meshwork. Arp 2/3 can only join onto previously existing microfilaments, but once bound it creates a site for the extension of new microfilaments, which creates branching (Weed, et al., 2000). Another molecule that is often found in polymerizing actin with Arp2/3 is cortactin
, which appears to link tyrosine kinase
signalling to cytoskeletal reorganization in the lamellipodium and its associated structures (ibid.).
Rac
and Cdc42
are two Rho
-family GTPase
s which are normally cytosol
ic but can also be found in the cell membrane under certain conditions (Small, et al., 2002). When Cdc42 is activated, it can interact with Wiskott-Aldrich syndrome
protein (WASp
) family receptors, in particular N-WASp, which then activates Arp2/3. This stimulates actin branching and increases cell motility
(Small, et al., 2002). Rac1 induces cortactin to localize to the cell membrane, where it simultaneously binds F-actin and Arp2/3. The result is a structural reorganization of the lamellipodium and ensuing cell motility (Weed, et al., 2000). Rac promotes lamellipodia while cdc42 promotes filopodia (Hall 1998).
Ena/VASP
proteins are found at the leading edge of lamellipodia, where they promote actin polymerization necessary for lamellipodial protrusion and chemotaxis. Further, Ena/VASP prevents the action of capping protein, which halts actin polymerization. (Bear and Gertler, 2009)
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
protein actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
projection on the mobile edge of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. It contains a quasi-two-dimensional actin mesh; the whole structure propels the cell across a substrate (Alberts, et al., 2002). Within the lamellipodia are ribs of actin called microspikes, which, when they spread beyond the lamellipodium frontier, are called filopodia
Filopodia
Filopodia are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. They contain actin filaments cross-linked into bundles by actin-binding proteins, e.g. fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking it to the...
(Small, et al., 2002). The lamellipodium is born of actin nucleation
Nucleation
Nucleation is the extremely localized budding of a distinct thermodynamic phase. Some examples of phases that may form by way of nucleation in liquids are gaseous bubbles, crystals or glassy regions. Creation of liquid droplets in saturated vapor is also characterized by nucleation...
in the plasma membrane of the cell (Alberts, et al., 2002) and is the primary area of actin incorporation or microfilament
Microfilament
Microfilaments are the thinnest filaments of the cytoskeleton, a structure found in the cytoplasm of all eukaryotic cells. These linear polymers of actin subunits are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton...
formation of the cell.
Lamellipodia are found primarily in very mobile cells, for example the keratinocytes of fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
and frog
Frog
Frogs are amphibians in the order Anura , formerly referred to as Salientia . Most frogs are characterized by a short body, webbed digits , protruding eyes and the absence of a tail...
s, which are involved in the quick repair of wounds
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
, crawling at a speeds of 10-20μm/minute over epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
surfaces. A lamellipodium separated from the main part of a cell by scratching across the cell with a pipette
Pipette
A pipette is a laboratory tool used to transport a measured volume of liquid.-Use and variations:Pipettes are commonly used in molecular biology, analytical chemistry as well as medical tests...
tip can continue to crawl freely about on its own.
Lamellipodia are a characteristic feature at the front, leading edge, of motile cells. They are believed to be the actual motor which pulls the cell forward during the process of cell migration
Cell migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations...
. The tip of the lamellipodium is the site where exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
occurs in migrating mammalian cells as part of their clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
-mediated endocytic cycle
Endocytic cycle
Most animal cells take up portions of their surface plasma membranes in a process called endocytosis. The main route of endocytosis is the coated pit, which buds into a cell to form a cytoplasmic vesicle — a clathrin-coated vesicle. The membrane so internalised is processed in a series of...
. This, together with actin-polymerisation there, helps extend the lamella forward and thus advance the cell's front. It thus acts as a steering device for cells in the process of chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
. It is also the site from which particles or aggregates attached to the cell surface migrate in a process known as cap formation
Cap formation
When molecules on the surface of a cell are crosslinked, they are moved to one end of the cell to form a “cap”. This phenomenon, the process of which is called cap formation, was discovered in 1971 on lymphocytes and is a property of amoebae and all locomotory animal cells except sperm. The...
.
Structurally, the barbed ends of the microfilaments (localized actin monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
s in an ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
-bound form) face the "seeking" edge of the cell, while the pointed ends (localized actin monomers in an ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
-bound form) face the lamella behind (Cramer, 1997). This creates treadmilling
Treadmilling
Treadmilling is a phenomenon observed in many cellular cytoskeletal filaments, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks resulting in a section of filament seemingly "moving" across a stratum or the cytosol...
throughout the lamellipodium, which aids in the retrograde flow of particles throughout (ibid.). Arp2/3 complex
Arp2/3 complex
Arp2/3 complex is a seven-subunit protein that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most in actin cytoskeleton-containing eukaryotic cells....
es are present at microfilament-microfilament junctions in lamellipodia, and help create the actin meshwork. Arp 2/3 can only join onto previously existing microfilaments, but once bound it creates a site for the extension of new microfilaments, which creates branching (Weed, et al., 2000). Another molecule that is often found in polymerizing actin with Arp2/3 is cortactin
Cortactin
Cortactin is a monomeric protein located in the cytoplasm of cells that can be activated by external stimuli to promote polymerization and rearrangement of the actin cytoskeleton, especially the actin cortex around the cellular periphery. It is present in all cell types...
, which appears to link tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
signalling to cytoskeletal reorganization in the lamellipodium and its associated structures (ibid.).
Rac
Rac (GTPase)
Rac is a subfamily of the Rho family of GTPases, small signaling G proteins .The subgroup include:*Rac1*Rac2*Rac3*RhoG...
and Cdc42
CDC42
Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
are two Rho
Rho
Rho is the 17th letter of the Greek alphabet. In the system of Greek numerals, it has a value of 100. It is derived from Semitic resh "head"...
-family GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
s which are normally cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
ic but can also be found in the cell membrane under certain conditions (Small, et al., 2002). When Cdc42 is activated, it can interact with Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome
Wiskott–Aldrich syndrome is a rare X-linked recessive disease characterized by eczema, thrombocytopenia , immune deficiency, and bloody diarrhea . It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954...
protein (WASp
WAsP
WAsP is a PC program for predicting wind climates, wind resources, and power productions from wind turbines and wind farms. The predictions are based on wind data measured at stations in the same region. The program includes a complex terrain flow model, a roughness change model, and a model for...
) family receptors, in particular N-WASp, which then activates Arp2/3. This stimulates actin branching and increases cell motility
Motility
Motility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
(Small, et al., 2002). Rac1 induces cortactin to localize to the cell membrane, where it simultaneously binds F-actin and Arp2/3. The result is a structural reorganization of the lamellipodium and ensuing cell motility (Weed, et al., 2000). Rac promotes lamellipodia while cdc42 promotes filopodia (Hall 1998).
Ena/VASP
Ena/Vasp homology proteins
ENA/VASP Homology proteins or EVH proteins are a family of closely related proteins involved in cell motility in vertebrate and invertebrate animals. EVH proteins are modular proteins that are involved in actin polymerisation, as well as interaction with other proteins...
proteins are found at the leading edge of lamellipodia, where they promote actin polymerization necessary for lamellipodial protrusion and chemotaxis. Further, Ena/VASP prevents the action of capping protein, which halts actin polymerization. (Bear and Gertler, 2009)