Filamin

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Filamins are a class of proteins that hold two actin filaments at large angles. [1] Filamin protein in mammals is made up of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules of roughly 95 amino acids. There are two hinge regions; between repeats 15-16 and 23-24. Filamin gets cleaved at these hinge regions to generate smaller fragments of the protein. Filamin has two actin-binding sites with a V-linkage between them, so that it cross-links actin filaments into a network with the filaments orientated almost at right angles to one another. [2]

Contents

Filamin proteins include:

Over-expression of FLNA stops the regeneration of bladder carcinoma (BC) cells, by inhibiting the cell cycle and inducing apoptosis of BC cells. [3] FLNA has also been shown to reduce the mobility and invasion abilities of BC cells. [3]

FLNA

The FLNa protein is also known for having an important structural function in the cardiovascular system. In particular, it has been studied by the American Society of Hematology for its role in platelet function in the blood. Platelets are known for their role in wound repair as they are able to aggregate and stop bleeding. Megakaryocytes allow for the production of platelets. However, mutations in the FLNa gene have been found to disrupt the process of healing as they limit the production of giant platelets that are needed for healing. [4] This condition is known as Macrothrombocytopenia.

FLNC

The FLNC protein is important to the functioning of cardiac and skeletal tissue. [5] In particular, mutations to the FLNC can have detrimental effects on cardiac tissue. The FLNC proteins have an important role in the structure of cardiac muscle. They contribute to the z-disk proteins which are heavily found in both cardiac and skeletal muscle tissue. [6] Many studies have been conducted to evaluate the effects of mutations on the FLNC gene to patients that are otherwise healthy in terms of their heart. Studies conducted by the American College of Cardiology Foundation show that missense mutations in the FLNC gene could be precursors for diverse cardiomyopathies. [7] Specifically, hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) were noted. A further investigation of the link between this protein and cardiac tissue could allow professionals to develop treatments to prevent and treat patients with FLNC mutation induced cardiomyopathies.

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<span class="mw-page-title-main">Desmosome</span> Cell junction involved in cell-to-cell adhesion

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<span class="mw-page-title-main">Arrhythmogenic cardiomyopathy</span> Medical condition

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<span class="mw-page-title-main">Desmin</span> Mammalian protein found in humans

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<span class="mw-page-title-main">Desmoglein-2</span> Protein found in humans

Desmoglein-2 is a protein that in humans is encoded by the DSG2 gene. Desmoglein-2 is highly expressed in epithelial cells and cardiomyocytes. Desmoglein-2 is localized to desmosome structures at regions of cell-cell contact and functions to structurally adhere adjacent cells together. In cardiac muscle, these regions are specialized regions known as intercalated discs. Mutations in desmoglein-2 have been associated with arrhythmogenic right ventricular cardiomyopathy and familial dilated cardiomyopathy.

<span class="mw-page-title-main">Desmoplakin</span> Protein found in humans

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

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

Nebulette is a cardiac-specific isoform belonging to the nebulin family of proteins. It is encoded by the NEBL gene. This family is composed of 5 members: nebulette, nebulin, N-RAP, LASP-1 and LASP-2. Nebulette localizes to Z-discs of cardiac muscle and appears to regulate the length of actin thin filaments.

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<span class="mw-page-title-main">Ryanodine receptor 2</span> Transport protein and coding gene in humans

Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.

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

Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene.

<span class="mw-page-title-main">ACTC1</span> Protein-coding gene in the species Homo sapiens

ACTC1 encodes cardiac muscle alpha actin. This isoform differs from the alpha actin that is expressed in skeletal muscle, ACTA1. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart.

<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">DSC2</span> Protein-coding gene in humans

Desmocollin-2 is a protein that in humans is encoded by the DSC2 gene. Desmocollin-2 is a cadherin-type protein that functions to link adjacent cells together in specialized regions known as desmosomes. Desmocollin-2 is widely expressed, and is the only desmocollin isoform expressed in cardiac muscle, where it localizes to intercalated discs. Mutations in DSC2 have been causally linked to arrhythmogenic right ventricular cardiomyopathy.

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

Filamin B, beta (FLNB), also known as Filamin B, beta , is a cytoplasmic protein which in humans is encoded by the FLNB gene.

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

Delta-sarcoglycan is a protein that in humans is encoded by the SGCD gene.

<span class="mw-page-title-main">MYH6</span> Protein-coding gene in the species Homo sapiens

Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.

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

Plakophilin-2 is a protein that in humans is encoded by the PKP2 gene. Plakophilin 2 is expressed in skin and cardiac muscle, where it functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiac muscle, plakophilin-2 is found in desmosome structures located within intercalated discs. Mutations in PKP2 have been shown to be causal in arrhythmogenic right ventricular cardiomyopathy.

<span class="mw-page-title-main">LDB3</span> Protein-coding gene in the species Homo sapiens

LIM domain binding 3 (LDB3), also known as Z-band alternatively spliced PDZ-motif (ZASP), is a protein which in humans is encoded by the LDB3 gene. ZASP belongs to the Enigma subfamily of proteins and stabilizes the sarcomere during contraction, through interactions with actin in cardiac and skeletal muscles. Mutations in the ZASP gene has been associated with several muscular diseases.

References

  1. ↑ Murray JT, Campbell DG, Peggie M, Mora A, Alfonso M, Cohen P (December 2004). "Identification of filamin C as a new physiological substrate of PKBalpha using KESTREL". The Biochemical Journal. 384 (Pt 3): 489–94. doi:10.1042/BJ20041058. PMC   1134134 . PMID   15461588.
  2. ↑ Alberts, Bruce, author University of California, San Francisco, USA (2017-08-07). Molecular Biology of the Cell. Garland Science. ISBN   978-1-317-56374-7. OCLC   1001364893.{{cite book}}: |last= has generic name (help)CS1 maint: multiple names: authors list (link)
  3. 1 2 Wang Z, Li C, Jiang M, Chen J, Yang M, Pu J (February 2018). "Filamin A (FLNA) regulates autophagy of bladder carcinoma cell and affects its proliferation, invasion and metastasis". International Urology and Nephrology. 50 (2): 263–273. doi:10.1007/s11255-017-1772-y. PMID   29288417. S2CID   3345382.
  4. ↑ Rosa, Jean-Philippe; Raslova, Hana; Bryckaert, Marijke (2019). "Filamin A: Key actor in platelet biology". Blood. 134 (16): 1279–1288. doi:10.1182/blood.2019000014. PMID   31471375 . Retrieved 2023-05-15.
  5. ↑ Begay, Rene L.; Graw, Sharon L.; Sinagra, Gianfranco; Asimaki, Angeliki; Rowland, Teisha J.; Slavov, Dobromir B.; Gowan, Katherine; Jones, Kenneth L.; Brun, Francesca; Merlo, Marco; Miani, Daniela; Sweet, Mary; Devaraj, Kalpana; Wartchow, Eric P.; Gigli, Marta (April 2018). "Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell–Cell Adhesion Structures". JACC: Clinical Electrophysiology. 4 (4): 504–514. doi:10.1016/j.jacep.2017.12.003. hdl: 11368/2935202 .
  6. ↑ Begay, Rene L.; Graw, Sharon L.; Sinagra, Gianfranco; Asimaki, Angeliki; Rowland, Teisha J.; Slavov, Dobromir B.; Gowan, Katherine; Jones, Kenneth L.; Brun, Francesca; Merlo, Marco; Miani, Daniela; Sweet, Mary; Devaraj, Kalpana; Wartchow, Eric P.; Gigli, Marta (April 2018). "Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell–Cell Adhesion Structures". JACC: Clinical Electrophysiology. 4 (4): 504–514. doi:10.1016/j.jacep.2017.12.003. hdl: 11368/2935202 .
  7. ↑ Begay, Rene L.; Graw, Sharon L.; Sinagra, Gianfranco; Asimaki, Angeliki; Rowland, Teisha J.; Slavov, Dobromir B.; Gowan, Katherine; Jones, Kenneth L.; Brun, Francesca; Merlo, Marco; Miani, Daniela; Sweet, Mary; Devaraj, Kalpana; Wartchow, Eric P.; Gigli, Marta (April 2018). "Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell–Cell Adhesion Structures". JACC: Clinical Electrophysiology. 4 (4): 504–514. doi:10.1016/j.jacep.2017.12.003. hdl: 11368/2935202 .
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