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ACTIN AND MYOSIN
It is thought that the eukaryotic cytoskeleton evolved before the nucleus in ancestral eukaryotes and was a prerequisite for the endosymbiotic event which resulted in the eukaryotic nucleus. The eukaryotic cytoskeleton is composed of actin filaments, microtubules, intermediate filaments, and motor proteins (Elmendorf, 2003).
The shape of cells, whether they be human neurons, human lung cells, mammalian intestinal cells with microvilli, or turtle blood cells (images above) have specific shapes determined by their cytoskeletons. Actin is a highly conserved cytoskeletal element in eukaryotes and is also expressed in the nucleus. While yeast possess only one known actin gene, multiple genes are known from all protozoa, plants, and animals studied (Hightower, 1986). .Actin proteins are highly conserved proteins which make up most of the eukaryotic cytoskeleton and can compose 10-20% of the total cellular protein. These thin filaments are involved in organelle transport, cell motility, and cytokinesis (OMIM).
Although actin was once though to be a feature of eukaryotic cells which distinguished then from bacteria, it is now known that bacteria possess several homologs of actin such as MreB and ParM which can polymerize into filaments (Mayer, 2003).
the shape of the cell and ParM functions in
the movement of intracellular structures, such as plasmids (Amos, 2004;
Egleman, 2003). MreB seems to form a bacterial filamentous cytoskeleton under
the cell membrane (Egelman, 2001). FtsA and FtsZ function in bacterial cytokinesis
and are homologs of actin
and tubulin which function in eukaryotic cytokinesis (van den Ent,
2001). In addition, there is evidence
that prokaryotes possess a “cytoskeletal web”
composed of filaments of EF-Tu, a protein which
eukaryotes uses solely as an elongation factor. EF-Tu can compose
9% of a bacterium’s protein (Mayer, 2003).
FtsA, MreB, MinD, and ParM are important components of the bacterial cytoskeleton that polymerize to perform a variety of functions including determining cell shape, protein localization, and DNA segregation.Their three dimensional structures are similar to those of actin despite differences in amino acid sequences. Another actin homolog, AlfA functions in plasmid segregation and sporulationLong filaments of the actin homolog MamK can stretch the length of bacterial cells. Most bacterial actin homologs form filaments (although that may not be true of FtsA) (Pogliano, 2008) In bacteria, homologs of actin segregate both plasmid (ParM) and chromosomal (MreB) DNA during cell division (Gerdes, 2004).
In eukaryotes, the “tilt” of actin subunits is important in determining subunit interaction in filaments. This tilt is determined by two inserted sequences which are absent in bacterial homologs (Egleman, 2003). All plant actins seem to be derived from a single actin gene in green algae (Kandasamy, ?). In virtually all known actins, the 73rd amino acid histidine is modified to 3 methyl histidine. This modification does not occur in amoebae and yeast (Kalhor, 1999).
Amphioxus uses muscle fibers in its notochord, using it for locomotion in a way unlike that of vertebrate embryos. The actin in amphioxus notochord is intermediate between the forms of actin used in muscle and non-muscle cells in vertebrates (Suzuki, 2000).
Actin has been highly conserved throughout evolution. The amino acid sequences of yeast actin and human muscle actin are 87% identical and there are no amino acid differences between the muscle actins of chickens and humans (Egelman, 2001). There see to be around 20 actin genes in the human genome.
ACTA1 is expressed in skeletal muscle and mutations cause myopathy.
ACTG1 is expressed in skeletal muscle cells and is part of the cytoskeleton elsewhere.
ACTG2 is expressed in smooth muscle (such as that of the uterus below).
|ACTC is expressed in cardiac muscle (heart muscle depicted below) and mutations can cause cardiomyopathy.|
ACTSA is expressed in smooth muscle and in the aorta. This gene possesses two introns not found in the genes expressed in cardiac or skeletal muscle.
ACTB is expressed in cells other than muscle. There are about 20 pseudogenes of ACTB (for example, ACTBP1-5).
ACTIN, platelet is expressed in platelets (the purple cell in the following image is a platelet).
The actin superfamily includes actin, actin related proteins (ARPs), heat shock proteins, heat shock protein cognates (HSP60, HSC70), sugar kinases (such as hexokinase), and a number of ATP-binding proteins known in bacteria (such as MreB, FtsA, and StbA) (Kandasamy, ?). Actin is conserved in the diverse classes of eukaryotes, as are actin-related proteins (ARPs). Some ARPs function in the cytoskeleton (ARP1-3) where two ARPs (ARP2 and ARP3) are required for the polymerization of actin monomers. A number of ARPs function in the nucleus where some of them have a role in remodeling chromatin. The fact that this role is conserved in eukaryotes indicates that ancestral eukaryotes utilized members of the actin family in the nucleus. ARP1, 2, 3, 4, 5, 6, 8,and 10 are known in humans and diverse other eukaryotes as well including plants and/or yeast. ARP 7 and ARP 9 are only known in yeast (Blessing, 2004).
ARP1 and ARP10 functions with dynein which functions in vesicle movement.
ARP4, ARP5, ARP6, ARP8, and ARP10 function in chromatin remodeling, often as part of a complex (such as SWI2/SNF2) (Blessing, 2004).
ACTIN RELATED PROTEINS
ACTIN RELATED PROTEINS
Actin and 11 families of actin-related proteins compose the actin superfamily which perform diverse functions in both the cytoplasm (such as determining cell structure, actin polymerization, dynein function) and nucleus (transcription, mRNA processing, gene activation, gene silencing, and restructuring of chromatin) (Chen, 2007). The actin related protein BAF53/ARPNβ is a component of a number of nuclear complexes such as SWI/SNF-related P-BAF complex, SWI2/SNF2-related p400 complexes, Tip60 histone acetyltransferase complex, and the cMyc-interacting nuclear complex. ArpNα participates in mammalian SWI/SNF complexes which remodel chromatin and regulate the expression of brain specific genes (some of which function in neural differentiation) (Kuroda, 2002). Nuclear ARPs also function in histone acetyltransferase complexes (HAT) (Kandasamy, ).
Myosins form a eukaryotic gene family whose were derived from a small number of ancestral myosins (perhaps three) possessed by ancestral eukaryotes (Foth, 2006). The myosin gene family is known in at least
6 phyla of protists and protest myosins include homologs of Myosin
I-A, I-B, I-C, I-D, I-E, I-F, I-K, II, IV, VII,
XI, XIV, Myo1, MyoJ, and MyoM. Protist myosins function in cell shape, motility, cytokinesis, nuclear division, and movement of membranes and
vacuoles(Gavin, 2001). Red algae and diplomonads lack myosin (Foth, 2006). No myosin gene is yet known in Giardia (Elmendorf, 2003). Mammals can possess 40 myosin genes (Foth, 2006).
Red algae and diplomonads lack myosin (Foth, 2006). No myosin gene is yet known in Giardia (Elmendorf, 2003). Mammals can possess 40 myosin genes (Foth, 2006).
Mammals can possess 40 myosin genes (Foth, 2006).
A number of cellular actions, such as motility, cytokinesis, and changes in cell shape utilize the actin cytoskeleton and myosin motors. Conventional myosin molecules, such as those found in muscle, are composed of two heavy chains (about 200 kDa) and 4 light chains (about 20 kDa). The light chains form alpha helices that compose the neck attached to the myosin “head”.
MYL1 can be spliced differently to produce alternate transcripts.
MYL2 is expressed in cardiac and smooth muscle; mutations cause hypertrophic cardiomyopathy.
MYL3 mutations cause hypertrophic cardiomyopathy.
MYL4 is expressed only during fetal development.
MYL5 is expressed in the retina (such as that of a developing frog in the following image), cerebellum, basal ganglia, and in fetal skeletal muscle.
Many of the heavy chain genes exist in a cluster on chromosome 17p13 (MYH3-MYH2-MYH1-MYH4-MYH8). This cluster corresponds to one on mouse chromosome 11.
MYH1 is expressed in skeletal muscle but functions in cytokinesis, vesicle transport, and cell locomotion in other cells.
MYH2 mutations cause inclusion body myopathy.
MYH3 is expressed in fetal muscle and after birth is expressed in regenerating muscle.
MYH4 is expressed in skeletal muscle (pictured below).
MYH7 and MYH6 are duplications of the same ancestral gene. MYH7 is upstream of MYH6 and is expressed during development while MYH6 is expressed later. Just as in the HOX and globin clusters, the order of expression is determined by the order is a cluster.
MYH8 is expressed around the time of birth and persists is some areas later in life such as the eye muscles, the masseter muscle, and regenerating muscles.
MYH9 mutations cause the May Hegglin Fechtner syndrome and the Sebastion syndrome whose symptoms may include deafness, cataracts, nephritis, and large platelets.
MYH10 is expressed in non-muscle cells.
MYH11 is expressed in smooth muscle (such as that from the gastrointestinal tract in the following image).
MYH13 is expressed primarily in eye muscles.
In vertebrates, the MYH16 is expressed only in chewing muscles and other muscles derived from the first pharyngeal arch. In addition to humans, a number of mammals have lost the expression of this heavy chain myosin (such as artiodactyls, rodents, and kangaroos) (McCollum, 2006).
Unconventional myosins are molecular motors which move along actin molecules using ATPase activity. Their tails vary, allowing them to attach to different molecules. Some myosins in amoeba (an amoeba is depicted in the following image) are particularly long-tailed. Unconventional myosins have been linked to unexpected functions such as differentiation and gene regulation (Redowicz, 2007).
Seven of the known 11 classes of unconventional myosin molecules are found in vertebrates. There are 11 classes of myosin molecules in the myosin superfamily that are known from animals, plants, fungi, and protists. Vertebrates have some myosins which are the predominant types found in amoeba. Some unconventional myosins are expressed at the brush border of the intestines (Mooseker, 1995). A number of unconventional myosin classes had already appeared in primitive eukaryotes such as classes I, V, VII, and XII (Baker, 1997).
MYO1C tails can interact with phospholipids and are involved in the movement of vesicles.
MYO1E is expressed throughout the body. One region at the C-terminus is homologous to the src gene, just as is observed in some protistan myosins.
MYO3A have kinase activity at their C-terminal and are expressed in photoreceptors and in the ear. Mutations can cause deafness.
MYO5A molecules are associated with the centrosome. Mutations in humans cause the Griscelli syndrome with its abnormal lymphocytes and macrophages (and ultimately death without a bone marrow transplant); mutations in mice cause convulsions and death.
MYO5B is expressed most highly in the liver (pictured below) and kidney.
MYO6 is widely expressed. Mutations can cause deafness.]
MYO7A mutations cause Usher syndrome type 1 with its deafness and retinitis pigmentosa.
MYO7B in mice is expressed in the intestine and kidney.
MYO9A is expressed in the nervous system, kidney, and thyroid in mice.
MYO9B is a single head myosin which moves in the opposite direction as other myosins.
MYO10 is present in pseudopods in cells performing phagocytosis.
MYO15A is homologous to the shaker-2 gene in mice. Mutations in humans cause deafness.
MYO18B is expressed in skeletal muscle, cardiac muscle, and the lung.
Myosins have been found which are limited to specific groups such as chordates (XIX), insects (XX), and four in certain protists (Goodson, 2006).
Mutations in myosin III genes affect human hearing and fly vision (Walsh, 2002).