Actin, cytoplasmic 2

Last updated
ACTG1
Protein ACTG1 PDB 1atn.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ACTG1 , ACT, ACTG, BRWS2, DFNA20, DFNA26, HEL-176, actin gamma 1
External IDs OMIM: 102560; MGI: 87906; HomoloGene: 74402; GeneCards: ACTG1; OMA:ACTG1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

71

11465

Ensembl

ENSG00000184009

ENSMUSG00000062825

UniProt

P63261

P63260

RefSeq (mRNA)

NM_001199954
NM_001614

NM_009609
NM_001313923

RefSeq (protein)

NP_001186883
NP_001605

NP_001300852
NP_033739

Location (UCSC) Chr 17: 81.51 – 81.52 Mb Chr 11: 120.24 – 120.24 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Actin, cytoplasmic 2, or gamma-actin is a protein that in humans is encoded by the ACTG1 gene. [5] Gamma-actin is widely expressed in cellular cytoskeletons of many tissues; in adult striated muscle cells, gamma-actin is localized to Z-discs and costamere structures, which are responsible for force transduction and transmission in muscle cells. Mutations in ACTG1 have been associated with nonsyndromic hearing loss and Baraitser-Winter syndrome, as well as susceptibility of adolescent patients to vincristine toxicity.

Contents

Structure

Human gamma-actin is 41.8 kDa in molecular weight and 375 amino acids in length. [6] Actins are highly conserved proteins that are involved in various types of cell motility, and maintenance of the cytoskeleton. In vertebrates, three main groups of actin paralogs, alpha, beta, and gamma, have been identified. [7]

The alpha actins are found in muscle tissues and are a major constituent of the sarcomere contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton, and as mediators of internal cell motility. Actin, gamma 1, encoded by this gene, is found in non-muscle cells in the cytoplasm, and in muscle cells at costamere structures, or transverse points of cell-cell adhesion that run perpendicular to the long axis of myocytes. [8] [9] [10]

Function

In myocytes, sarcomeres adhere to the sarcolemma via costameres, which align at Z-discs and M-lines. [11] The two primary cytoskeletal components of costameres are desmin intermediate filaments and gamma-actin microfilaments. [12] It has been shown that gamma-actin interacting with another costameric protein dystrophin is critical for costameres forming mechanically strong links between the cytoskeleton and the sarcolemmal membrane. [13] [14] Additional studies have shown that gamma-actin colocalizes with alpha-actinin and GFP-labeled gamma actin localized to Z-discs, whereas GFP-alpha-actin localized to pointed ends of thin filaments, indicating that gamma actin specifically localizes to Z-discs in striated muscle cells. [15] [16] [17]

During development of myocytes, gamma actin is thought to play a role in the organization and assembly of developing sarcomeres, evidenced in part by its early colocalization with alpha-actinin. [18] Gamma-actin is eventually replaced by sarcomeric alpha-actin isoforms, [19] [20] [21] with low levels of gamma-actin persisting in adult myocytes which associate with Z-disc and costamere domains. [15] [22] [23]

Insights into the function of gamma-actin in muscle have come from studies employing transgenesis. In a skeletal muscle-specific knockout of gamma-actin in mice, these animals showed no detectable abnormalities in development; however, knockout mice showed muscle weakness and fiber necrosis, along with decreased isometric twitch force, disrupted intrafibrillar and interfibrillar connections among myocytes, and myopathy. [24]

Clinical significance

An autosomal dominant mutation in ACTG1 in the DFNA20/26 locus at 17q25-qter was identified in patients with hearing loss. A Thr278Ile mutation was identified in helix 9 of gamma-actin protein, which is predicted to alter protein structure. This study identified the first disease causing mutation in gamma-actin and underlies the importance of gamma-actin as structural elements of the inner ear hair cells. [25] Since then, other ACTG1 mutations have been linked to nonsyndromic hearing loss, including Met305Thr. [26]

A missense mutation in ACTG1 at Ser155Phe has also been identified in patients with Baraitser-Winter syndrome, which is a developmental disorder characterized by congenital ptosis, excessively-arched eyebrows, hypertelorism, ocular colobomata, lissencephaly, short stature, seizures and hearing loss. [27] [28]

Differential expression of ACTG1 mRNA was also identified in patients with Sporadic Amyotrophic Lateral Sclerosis, a devastating disease with unknown causality, using a sophisticated bioinformatics approach employing Affymetrix long-oligonucleotide BaFL methods. [29]

Single nucleotide polymorphisms in ACTG1 have been associated with vincristine toxicity, which is part of the standard treatment regimen for childhood acute lymphoblastic leukemia. Neurotoxicity was more frequent in patients that were ACTG1 Gly310Ala mutation carriers, suggesting that this may play a role in patient outcomes from vincristine treatment. [30]

Interactions

ACTG1 has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.

<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">Intermediate filament</span> Cytoskeletal structure

Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate Branchiostoma.

<span class="mw-page-title-main">Vinculin</span> Mammalian protein found in Homo sapiens

In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane.

<span class="mw-page-title-main">Spectrin</span> Cytoskeletal protein

Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure. The hexagonal arrangements are formed by tetramers of spectrin subunits associating with short actin filaments at either end of the tetramer. These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh. The protein is named spectrin since it was first isolated as a major protein component of human red blood cells which had been treated with mild detergents; the detergents lysed the cells and the hemoglobin and other cytoplasmic components were washed out. In the light microscope the basic shape of the red blood cell could still be seen as the spectrin-containing submembranous cytoskeleton preserved the shape of the cell in outline. This became known as a red blood cell "ghost" (spectre), and so the major protein of the ghost was named spectrin.

<span class="mw-page-title-main">Plectin</span> Mammalian protein found in Homo sapiens

Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleton to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together, plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues.

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

Paxillin is a protein that in humans is encoded by the PXN gene. Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. Mutations in PXN as well as abnormal expression of paxillin protein has been implicated in the progression of various cancers.

<span class="mw-page-title-main">Costamere</span> Component of striated muscle cells

The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane.

<span class="mw-page-title-main">Protein 4.1</span> Protein-coding gene in the species Homo sapiens

Protein 4.1,, is a protein associated with the cytoskeleton that in humans is encoded by the EPB41 gene. Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Protein 4.1 interacts with spectrin and short actin filaments to form the erythrocyte membrane skeleton. Mutations of spectrin and protein 4.1 are associated with elliptocytosis or spherocytosis and anemia of varying severity.

<span class="mw-page-title-main">Integrin beta 1</span> Mammalian protein found in Homo sapiens

Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.

Dystrobrevin is a protein that binds to dystrophin in the costamere of skeletal muscle cells. In humans, there are at least two isoforms of dystrobrevin, dystrobrevin alpha and dystrobrevin beta.

<span class="mw-page-title-main">Actin, alpha skeletal muscle</span> Protein-coding gene in the species Homo sapiens

Actin, alpha skeletal muscle is a protein that in humans is encoded by the ACTA1 gene.

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

Actin beta is one of six different actin isoforms which have been identified in humans. This is one of the two nonmuscle cytoskeletal actins. Actins are highly conserved proteins that are involved in cell motility, structure and integrity. Alpha actins are a major constituent of the contractile apparatus.

<span class="mw-page-title-main">Alpha-actinin-2</span> Protein-coding gene in the species Homo sapiens

Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.

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

Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a protein that in humans is encoded by the FLNC gene. Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.

<span class="mw-page-title-main">ACTG2</span> Protein-coding gene in the species Homo sapiens

Actin, gamma-enteric smooth muscle is a protein that in humans is encoded by the ACTG2 gene.

<span class="mw-page-title-main">MYOT</span> Mammalian protein found in Homo sapiens

Myotilin is a protein that in humans is encoded by the MYOT gene. Myotilin also known as TTID is a muscle protein that is found within the Z-disc of sarcomeres.

<span class="mw-page-title-main">CSRP3</span> Protein-coding gene in the species Homo sapiens

Cysteine and glycine-rich protein 3 also known as cardiac LIM protein (CLP) or muscle LIM protein (MLP) is a protein that in humans is encoded by the CSRP3 gene.

<span class="mw-page-title-main">TLN1</span> Protein-coding gene in the species Homo sapiens

Talin-1 is a protein that in humans is encoded by the TLN1 gene. Talin-1 is ubiquitously expressed, and is localized to costamere structures in cardiac and skeletal muscle cells, and to focal adhesions in smooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage of integrins to the actin cytoskeleton and in the activation of integrins. Altered expression of talin-1 has been observed in patients with heart failure, however no mutations in TLN1 have been linked with specific diseases.

<span class="mw-page-title-main">TLN2</span> Protein-coding gene in the species Homo sapiens

Talin-2 is a protein in humans that is encoded by the TLN2 gene. It belongs to the talin protein family. This gene encodes a protein related to talin-1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments. Talin-2 is expressed at high levels in cardiac muscle and functions to provide linkages between the extracellular matrix and actin cytoskeleton at costamere structures to transduce force laterally.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000184009 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000062825 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: ACTG1 actin, gamma 1".
  6. ↑ "Protein sequence for human ACTG1 (Uniprot ID: P63261)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 21 July 2015. Retrieved 18 July 2015.
  7. ↑ Rubenstein PA (Jul 1990). "The functional importance of multiple actin isoforms". BioEssays. 12 (7): 309–15. doi:10.1002/bies.950120702. PMID   2203335. S2CID   2163289.
  8. ↑ Craig SW, Pardo JV (1983). "Gamma actin, spectrin, and intermediate filament proteins colocalize with vinculin at costameres, myofibril-to-sarcolemma attachment sites". Cell Motility. 3 (5–6): 449–62. doi:10.1002/cm.970030513. PMID   6420066.
  9. ↑ Pardo JV, Siliciano JD, Craig SW (Feb 1983). "A vinculin-containing cortical lattice in skeletal muscle: transverse lattice elements ("costameres") mark sites of attachment between myofibrils and sarcolemma". Proceedings of the National Academy of Sciences of the United States of America. 80 (4): 1008–12. Bibcode:1983PNAS...80.1008P. doi: 10.1073/pnas.80.4.1008 . PMC   393517 . PMID   6405378.
  10. ↑ Danowski BA, Imanaka-Yoshida K, Sanger JM, Sanger JW (Sep 1992). "Costameres are sites of force transmission to the substratum in adult rat cardiomyocytes". The Journal of Cell Biology. 118 (6): 1411–20. doi:10.1083/jcb.118.6.1411. PMC   2289604 . PMID   1522115.
  11. ↑ Clark KA, McElhinny AS, Beckerle MC, Gregorio CC (2002). "Striated muscle cytoarchitecture: an intricate web of form and function". Annual Review of Cell and Developmental Biology. 18: 637–706. doi:10.1146/annurev.cellbio.18.012502.105840. PMID   12142273.
  12. ↑ Kee AJ, Gunning PW, Hardeman EC (2009). "Diverse roles of the actin cytoskeleton in striated muscle". Journal of Muscle Research and Cell Motility. 30 (5–6): 187–97. doi:10.1007/s10974-009-9193-x. PMID   19997772. S2CID   6632615.
  13. 1 2 Rybakova IN, Patel JR, Ervasti JM (Sep 2000). "The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin". The Journal of Cell Biology. 150 (5): 1209–14. doi:10.1083/jcb.150.5.1209. PMC   2175263 . PMID   10974007.
  14. ↑ Ervasti JM (Apr 2003). "Costameres: the Achilles' heel of Herculean muscle". The Journal of Biological Chemistry. 278 (16): 13591–4. doi: 10.1074/jbc.R200021200 . PMID   12556452.
  15. 1 2 Nakata T, Nishina Y, Yorifuji H (Aug 2001). "Cytoplasmic gamma actin as a Z-disc protein". Biochemical and Biophysical Research Communications. 286 (1): 156–63. doi:10.1006/bbrc.2001.5353. PMID   11485322.
  16. ↑ Papponen H, Kaisto T, Leinonen S, Kaakinen M, Metsikkö K (Jan 2009). "Evidence for gamma-actin as a Z disc component in skeletal myofibers". Experimental Cell Research. 315 (2): 218–25. doi:10.1016/j.yexcr.2008.10.021. PMID   19013151.
  17. ↑ Vlahovich N, Kee AJ, Van der Poel C, Kettle E, Hernandez-Deviez D, Lucas C, Lynch GS, Parton RG, Gunning PW, Hardeman EC (Jan 2009). "Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle". Molecular Biology of the Cell. 20 (1): 400–9. doi:10.1091/mbc.E08-06-0616. PMC   2613127 . PMID   19005216.
  18. ↑ Lloyd CM, Berendse M, Lloyd DG, Schevzov G, Grounds MD (Jul 2004). "A novel role for non-muscle gamma-actin in skeletal muscle sarcomere assembly". Experimental Cell Research. 297 (1): 82–96. doi:10.1016/j.yexcr.2004.02.012. PMID   15194427.
  19. ↑ Schwartz RJ, Rothblum KN (Jul 1981). "Gene switching in myogenesis: differential expression of the chicken actin multigene family". Biochemistry. 20 (14): 4122–9. doi:10.1021/bi00517a027. PMID   7284314.
  20. ↑ Shani M, Zevin-Sonkin D, Saxel O, Carmon Y, Katcoff D, Nudel U, Yaffe D (Sep 1981). "The correlation between the synthesis of skeletal muscle actin, myosin heavy chain, and myosin light chain and the accumulation of corresponding mRNA sequences during myogenesis". Developmental Biology. 86 (2): 483–92. doi:10.1016/0012-1606(81)90206-2. PMID   7286410.
  21. ↑ von Arx P, Bantle S, Soldati T, Perriard JC (Dec 1995). "Dominant negative effect of cytoplasmic actin isoproteins on cardiomyocyte cytoarchitecture and function". The Journal of Cell Biology. 131 (6 Pt 2): 1759–73. doi:10.1083/jcb.131.6.1759. PMC   2120671 . PMID   8557743.
  22. ↑ Hanft LM, Bogan DJ, Mayer U, Kaufman SJ, Kornegay JN, Ervasti JM (Jul 2007). "Cytoplasmic gamma-actin expression in diverse animal models of muscular dystrophy". Neuromuscular Disorders. 17 (7): 569–74. doi:10.1016/j.nmd.2007.03.004. PMC   1993539 . PMID   17475492.
  23. ↑ Kee AJ, Schevzov G, Nair-Shalliker V, Robinson CS, Vrhovski B, Ghoddusi M, Qiu MR, Lin JJ, Weinberger R, Gunning PW, Hardeman EC (Aug 2004). "Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy". The Journal of Cell Biology. 166 (5): 685–96. doi:10.1083/jcb.200406181. PMC   2172434 . PMID   15337777.
  24. ↑ Sonnemann KJ, Fitzsimons DP, Patel JR, Liu Y, Schneider MF, Moss RL, Ervasti JM (Sep 2006). "Cytoplasmic gamma-actin is not required for skeletal muscle development but its absence leads to a progressive myopathy". Developmental Cell. 11 (3): 387–97. doi: 10.1016/j.devcel.2006.07.001 . PMID   16950128.
  25. ↑ van Wijk E, Krieger E, Kemperman MH, De Leenheer EM, Huygen PL, Cremers CW, Cremers FP, Kremer H (Dec 2003). "A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)". Journal of Medical Genetics. 40 (12): 879–84. doi:10.1136/jmg.40.12.879. PMC   1735337 . PMID   14684684.
  26. ↑ Park G, Gim J, Kim AR, Han KH, Kim HS, Oh SH, Park T, Park WY, Choi BY (18 March 2013). "Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family". BMC Genomics. 14: 191. doi: 10.1186/1471-2164-14-191 . PMC   3608096 . PMID   23506231.
  27. ↑ Rivière JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB (Apr 2012). "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome". Nature Genetics. 44 (4): 440–4, S1–2. doi:10.1038/ng.1091. PMC   3677859 . PMID   22366783.
  28. ↑ Di Donato N, Rump A, Koenig R, Der Kaloustian VM, Halal F, Sonntag K, Krause C, Hackmann K, Hahn G, Schrock E, Verloes A (Feb 2014). "Severe forms of Baraitser-Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations". European Journal of Human Genetics. 22 (2): 179–83. doi:10.1038/ejhg.2013.130. PMC   3895648 . PMID   23756437.
  29. ↑ Baciu C, Thompson KJ, Mougeot JL, Brooks BR, Weller JW (24 September 2012). "The LO-BaFL method and ALS microarray expression analysis". BMC Bioinformatics. 13: 244. doi: 10.1186/1471-2105-13-244 . PMC   3526454 . PMID   23006766.
  30. ↑ Ceppi F, Langlois-Pelletier C, Gagné V, Rousseau J, Ciolino C, De Lorenzo S, Kevin KM, Cijov D, Sallan SE, Silverman LB, Neuberg D, Kutok JL, Sinnett D, Laverdière C, Krajinovic M (Jun 2014). "Polymorphisms of the vincristine pathway and response to treatment in children with childhood acute lymphoblastic leukemia". Pharmacogenomics. 15 (8): 1105–16. doi:10.2217/pgs.14.68. PMC   4443746 . PMID   25084203.
  31. ↑ Hubberstey A, Yu G, Loewith R, Lakusta C, Young D (Jun 1996). "Mammalian CAP interacts with CAP, CAP2, and actin". Journal of Cellular Biochemistry. 61 (3): 459–66. doi:10.1002/(SICI)1097-4644(19960601)61:3<459::AID-JCB13>3.0.CO;2-E. PMID   8761950. S2CID   46076387.
  32. ↑ Hertzog M, van Heijenoort C, Didry D, Gaudier M, Coutant J, Gigant B, Didelot G, Préat T, Knossow M, Guittet E, Carlier MF (May 2004). "The beta-thymosin/WH2 domain; structural basis for the switch from inhibition to promotion of actin assembly". Cell. 117 (5): 611–23. doi: 10.1016/S0092-8674(04)00403-9 . PMID   15163409. S2CID   8628287.
  33. ↑ Van Troys M, Dewitte D, Goethals M, Carlier MF, Vandekerckhove J, Ampe C (Jan 1996). "The actin binding site of thymosin beta 4 mapped by mutational analysis". The EMBO Journal. 15 (2): 201–10. doi:10.1002/j.1460-2075.1996.tb00350.x. PMC   449934 . PMID   8617195.
  34. ↑ Hijikata T, Nakamura A, Isokawa K, Imamura M, Yuasa K, Ishikawa R, Kohama K, Takeda S, Yorifuji H (Jun 2008). "Plectin 1 links intermediate filaments to costameric sarcolemma through beta-synemin, alpha-dystrobrevin and actin". Journal of Cell Science. 121 (Pt 12): 2062–74. doi:10.1242/jcs.021634. PMID   18505798. S2CID   207164281.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.