CSRP3

From Wikipedia, the free encyclopedia
Jump to: navigation, search
CSRP3
Protein CSRP3 PDB 2O10.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CSRP3, CLP, CMD1M, CMH12, CRP3, LMO4, MLP, cysteine and glycine rich protein 3
External IDs MGI: 1330824 HomoloGene: 20742 GeneCards: CSRP3
RNA expression pattern
PBB GE CSRP3 205553 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003476

NM_001198841
NM_013808

RefSeq (protein)

NP_003467

NP_001185770.1
NP_038836.1
NP_001185770
NP_038836

Location (UCSC) Chr 11: 19.18 – 19.21 Mb Chr 7: 48.83 – 48.85 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Cysteine and glycine-rich protein 3 gene codes for the Muscle LIM Protein (MLP) or CSRP3, a small 194 amino acid protein, which is specifically expressed in skeletal muscles and cardiac muscle.[3][4] Since the identification of MLP, 20 years ago,[5] a multitude of studies have focused on delineating its functional significance.

Gene[edit]

The CSRP3 gene was discovered in rat in 1994.[5] In humans it was mapped to chromosome 11p15.1,[6][7] where it spans a 20kb genomic region, organized in 6 exons. The full length transcript is 0.8kb,[6][8] while a splice variant, originating from the alternative splicing of exons 3 and 4, was recently identified and designated MLP-b.[9]

Structure[edit]

MLP contains two LIM domains (LIM1 and LIM2), each being surrounded by glycine-rich regions, and the two separated by more than 50 residues.[10] LIM domains offer a remarkable ability for protein-protein interactions.[11] Furthermore, MLP carries a nuclear localization signal at amino acid positions 64-69 [12] MLP can be acetylated/deacetylated at the position 69 lysine residue (K69), by acetyltransferase (PCAF) and histone deacetylase 4 (HDAC4), respectively.[13] In myocytes, MLP has the ability to oligomerize, forming dimers, trimers and tetramers, an attribute that impacts its interactions, localization and function.[14]

Protein interactions and localization[edit]

MLP has been identified to bind to an increasing list of proteins, exhibiting variable subcellular localization and diverse functional properties. In particular, MLP interacts with proteins at the:

  1. Z-line, including telethonin (T-cap), alpha-actinin (ACTN), cofilin-2 (CFL2), calcineurin, HDAC4, MLP-b as well as to MLP itself;[8][9][13][15][16][17][18]
  2. costameres, where it binds to zyxin, integrin linked kinase (ILK) and beta1-spectrin;[15][19][20]
  3. intercalated discs, where it associates with the nebulin-related anchoring protein (NRAP);[21]
  4. nucleus, where it binds to the transcription factors MyoD, myogenin and MRF4.[22]

M-line as well as plasma membrane localization of MLP has also been observed, however, the protein associations mediating this subcellular distribution are currently unknown.[14][23] These diverse localization patterns and binding partners of MLP suggest a multitude of roles relating both to the striated myocyte cytoskeleton and the nucleus.[24] The role of MLP in each of these two cellular compartments appears to be dynamic, with studies demonstrating nucleocytoplasmic shuttling, driven by its nuclear localization signal, over time and under different conditions.[24]

Functions[edit]

In the nucleus, MLP acts as a positive regulator of myogenesis and promotes myogenic differentiation.[5] Overexpression of MLP enhances myotube differentiation, an effect attributed to the direct association of MLP with muscle specific transcription factors such as MyoD, myogenin and MRF4 and consequently the transcriptional control of fundamental muscle-specific genes.[5][9][22] In the cytoplasm, MLP is an important scaffold protein, implicated in various cytoskeletal macromolecular complexes, at the sarcomeric Z-line, the costameres, and the microfilaments.[8][9][13][15][16][17][18] At the Z-line, MLP interacts with different Z-line components [8][9][13][15][16][17][18][25][26] and acts as a scaffold protein promoting the assembly of macromolecular complexes along sarcomeres and actin-based cytoskeleton [8][19][21][27][28] Moreover, since the Z-line acts as a stretch sensor,[29][30][31][32] MLP is believed to be involved in mechano-signaling processes. Indeed, cardiomyocytes from MLP transgenic or knock-out mouse exhibit defective intrinsic stretch responses, due to selective loss of passive stretch sensing.[8][23] At the costameres, another region implicated in force transmission, MLP is thought to be contributing in mechanosensing through its interactions with β1 spectrin and zyxin. However, the precise role of MLP at the costameres has not been extensively investigated yet.

At the microfilaments, MLP is implicated in actin remodeling (or actin dynamics) through its interaction with cofilin-2 (CFL2). Binding of MLP to CFL2 enhances the CFL2-dependent F-actin depolymerization,[16] with a recent study demonstrating that MLP can act directly on actin cytoskeleton dynamics through direct binding that stabilizes and crosslinks actin filaments into bundles.[33]

Additionally, MLP is indirectly related to calcium homeostasis and energy metabolism. Specifically, acetylation of MLP increases the calcium sensitivity of myofilaments and regulates contractility,[13] while the absence of MLP causes alterations in calcium signaling (intracellular calcium handling) with defects in excitation-contraction coupling.[34][35][36] Furthermore, lack of MLP leads to local loss of mitochondria and energy deficiency.[37]

Clinical significance[edit]

MLP is directly associated with striated muscle diseases. Mutations in the CSRP3 gene have been detected in patients with dilated cardiomyopathy (DCM) [e.g. G72R and K69R], and hypertrophic cardiomyopathy (HCM) [e.g. L44P, S46R, S54R/E55G, C58G, R64C, Y66C, Q91L, K42/fs165], while the most frequent MLP mutation, W4R, has been found in both of these patient populations.[8][12][23][38][39][40][41] Biochemical and functional studies have been performed for some of these mutant proteins, and reveal aberrant localization and interaction patterns, leading to impaired molecular and cellular functions. For example, the W4R mutation abolishes the MLP/T-cap interaction, leading to mislocalization of T-cap, Z-line instability and severe sarcomeric structural defects.[8] The C58G mutation causes reduced protein stability due to enhanced ubiquitin-dependent proteasome degradation[38] while the K69L mutation, which is within the predicted nuclear localization signal of MLP, abolishes the MLP/α-actinin interaction and causes altered subcellular distribution of the mutant protein, showing predominant perinuclear localization.[41] Alterations in the protein expression levels of MLP, its oligomerization or splicing have also been described in human cardiac and skeletal muscle diseases: both MLP protein levels and oligomerization are down-regulated in human heart failure,[14][17] while MLP levels are significantly changed in different skeletal myopathies, including facioscapulohumeral muscular dystrophy, nemaline myopathy and limb girdle muscular dystrophy type 2B.[42][43][44] Moreover, significant changes in MLP-b protein expression levels, as well as deregulation of the MLP:MLP-b ratio have been detected in limb girdle muscular dystrophy type 2A, Duchenne muscular dystrophy and dermatomyositis patients.[9]

Animal models[edit]

Animal models are providing valuable insight on MLP’s functional significance in striated muscle pathophysiology. Ablation of Mlp (MLP-/-) in mice affects all striated muscles, although the cardiac phenotype is more severe, leading to alterations in cardiac pressure and volume, aberrant contractility, development of dilated cardiomyopathy with hypertrophy and progressive heart failure.[28][34][45] At the histological level there is dramatic disruption of the cardiomyocyte cytoarchitecture at multiple levels, and pronounced fibrosis.[21][28][36][46] Other cellular changes included alterations in intracellular calcium handling, local loss of mitochondria and energy deficiency.[34][35][36] Crossing MLP-/- mice with phospholamban (PLN) -/-, or β2-adrenergic receptor (β2-AR) -/-, or angiotensin II type 1a receptor (AT1a) -/-, or β-adrenergic receptor kinase 1 inhibitor (bARK1) -/- mice, as well as overexpressing calcineurin rescued their cardiac function, through a series of only partly understood molecular mechanisms.[47][48][49][50][51] Conversely crossing MLP-/- mice with β1-adrenergic receptor (β1-AR) -/- mice was lethal, while crossing MLP-/- mice with calcineurin -/- mice, enhanced fibrosis and cardiomyopathy.[47][48] A gene knockin mouse model harboring the human MLP-W4R mutation developed HCM and heart failure, while ultrastructural analysis of its cardiac tissue revealed myocardial disarray and significant fibrosis, increased nuclear localization of MLP concomitantly with reduced sarcomeric Z-line distribution.[23] Alterations in MLP nucleocytoplasmic shuttling, which are possibly modulated by changes in its oligomerization status, have also been implicated in hypertrophy and heart failure, independently of mutations.[14][24] Studies in Drosophila revealed that genetic ablation of Mlp84B, the Drosophila homolog of MLP, was associated with pupal lethality and impaired muscle function.[25] Mechanical studies of Mlp84B-null flight muscles indicate that loss of Mlp84B results in decreased muscle stiffness and power generation.[52] Cardiac-specific ablation of Mlp84B caused decreased lifespan, impaired diastolic function and disturbances in cardiac rhythm.[53] Overall, these animal models have provided critical evidence on the functional significance of MLP in striated muscle physiology and pathophysiology.

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Gehmlich K, Geier C, Milting H, Fürst D, Ehler E (2008). "Back to square one: what do we know about the functions of muscle LIM protein in the heart?". Journal of Muscle Research and Cell Motility. 29 (6–8): 155–8. doi:10.1007/s10974-008-9159-4. PMID 19115046. 
  4. ^ Knöll R, Hoshijima M, Chien KR (2001). "Muscle LIM protein in heart failure". Experimental and Clinical Cardiology. 7 (2–3): 104–5. PMC 2719181Freely accessible. PMID 19649232. 
  5. ^ a b c d Arber S, Halder G, Caroni P (Oct 1994). "Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation". Cell. 79 (2): 221–31. doi:10.1016/0092-8674(94)90192-9. PMID 7954791. 
  6. ^ a b Fung YW, Wang R, Liew CC (Jun 1996). "Characterization of a human cardiac gene which encodes for a LIM domain protein and is developmentally expressed in myocardial development". Journal of Molecular and Cellular Cardiology. 28 (6): 1203–10. doi:10.1006/jmcc.1996.0111. PMID 8782062. 
  7. ^ Fung YW, Wang RX, Heng HH, Liew CC (Aug 1995). "Mapping of a human LIM protein (CLP) to human chromosome 11p15.1 by fluorescence in situ hybridization". Genomics. 28 (3): 602–3. doi:10.1006/geno.1995.1200. PMID 7490106. 
  8. ^ a b c d e f g h Knöll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR (Dec 2002). "The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy". Cell. 111 (7): 943–55. doi:10.1016/s0092-8674(02)01226-6. PMID 12507422. 
  9. ^ a b c d e f Vafiadaki E, Arvanitis DA, Papalouka V, Terzis G, Roumeliotis TI, Spengos K, Garbis SD, Manta P, Kranias EG, Sanoudou D (Jul 2014). "Muscle lim protein isoform negatively regulates striated muscle actin dynamics and differentiation". The FEBS Journal. 281 (14): 3261–79. doi:10.1111/febs.12859. PMC 4416226Freely accessible. PMID 24860983. 
  10. ^ Weiskirchen R, Pino JD, Macalma T, Bister K, Beckerle MC (Dec 1995). "The cysteine-rich protein family of highly related LIM domain proteins". The Journal of Biological Chemistry. 270 (48): 28946–54. doi:10.1074/jbc.270.48.28946. PMID 7499425. 
  11. ^ Buyandelger B, Ng KE, Miocic S, Piotrowska I, Gunkel S, Ku CH, Knöll R (Jul 2011). "MLP (muscle LIM protein) as a stress sensor in the heart". Pflügers Archiv. 462 (1): 135–42. doi:10.1007/s00424-011-0961-2. PMC 3114083Freely accessible. PMID 21484537. 
  12. ^ a b Bos JM, Poley RN, Ny M, Tester DJ, Xu X, Vatta M, Towbin JA, Gersh BJ, Ommen SR, Ackerman MJ (May 2006). "Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin". Molecular Genetics and Metabolism. 88 (1): 78–85. doi:10.1016/j.ymgme.2005.10.008. PMC 2756511Freely accessible. PMID 16352453. 
  13. ^ a b c d e Gupta MP, Samant SA, Smith SH, Shroff SG (Apr 2008). "HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity". The Journal of Biological Chemistry. 283 (15): 10135–46. doi:10.1074/jbc.M710277200. PMC 2442284Freely accessible. PMID 18250163. 
  14. ^ a b c d Boateng SY, Belin RJ, Geenen DL, Margulies KB, Martin JL, Hoshijima M, de Tombe PP, Russell B (Jan 2007). "Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution and amounts of oligomeric muscle LIM protein". American Journal of Physiology. Heart and Circulatory Physiology. 292 (1): H259–69. doi:10.1152/ajpheart.00766.2006. PMID 16963613. 
  15. ^ a b c d Louis HA, Pino JD, Schmeichel KL, Pomiès P, Beckerle MC (Oct 1997). "Comparison of three members of the cysteine-rich protein family reveals functional conservation and divergent patterns of gene expression". The Journal of Biological Chemistry. 272 (43): 27484–91. doi:10.1074/jbc.272.43.27484. PMID 9341203. 
  16. ^ a b c d Papalouka V, Arvanitis DA, Vafiadaki E, Mavroidis M, Papadodima SA, Spiliopoulou CA, Kremastinos DT, Kranias EG, Sanoudou D (Nov 2009). "Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle". Molecular and Cellular Biology. 29 (22): 6046–58. doi:10.1128/MCB.00654-09. PMC 2772566Freely accessible. PMID 19752190. 
  17. ^ a b c d Zolk O, Caroni P, Böhm M (Jun 2000). "Decreased expression of the cardiac LIM domain protein MLP in chronic human heart failure". Circulation. 101 (23): 2674–7. doi:10.1161/01.cir.101.23.2674. PMID 10851202. 
  18. ^ a b c Heineke J, Ruetten H, Willenbockel C, Gross SC, Naguib M, Schaefer A, Kempf T, Hilfiker-Kleiner D, Caroni P, Kraft T, Kaiser RA, Molkentin JD, Drexler H, Wollert KC (Feb 2005). "Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc". Proceedings of the National Academy of Sciences of the United States of America. 102 (5): 1655–60. doi:10.1073/pnas.0405488102. PMC 547821Freely accessible. PMID 15665106. 
  19. ^ a b Flick MJ, Konieczny SF (May 2000). "The muscle regulatory and structural protein MLP is a cytoskeletal binding partner of betaI-spectrin". Journal of Cell Science. 113 (9): 1553–64. PMID 10751147. 
  20. ^ Postel R, Vakeel P, Topczewski J, Knöll R, Bakkers J (Jun 2008). "Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex". Developmental Biology. 318 (1): 92–101. doi:10.1016/j.ydbio.2008.03.024. PMID 18436206. 
  21. ^ a b c Ehler E, Horowits R, Zuppinger C, Price RL, Perriard E, Leu M, Caroni P, Sussman M, Eppenberger HM, Perriard JC (May 2001). "Alterations at the intercalated disk associated with the absence of muscle LIM protein". The Journal of Cell Biology. 153 (4): 763–72. doi:10.1083/jcb.153.4.763. PMC 2192386Freely accessible. PMID 11352937. 
  22. ^ a b Kong Y, Flick MJ, Kudla AJ, Konieczny SF (Aug 1997). "Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD". Molecular and Cellular Biology. 17 (8): 4750–60. doi:10.1128/mcb.17.8.4750. PMC 232327Freely accessible. PMID 9234731. 
  23. ^ a b c d Knöll R, Kostin S, Klede S, Savvatis K, Klinge L, Stehle I, Gunkel S, Kötter S, Babicz K, Sohns M, Miocic S, Didié M, Knöll G, Zimmermann WH, Thelen P, Bickeböller H, Maier LS, Schaper W, Schaper J, Kraft T, Tschöpe C, Linke WA, Chien KR (Mar 2010). "A common MLP (muscle LIM protein) variant is associated with cardiomyopathy". Circulation Research. 106 (4): 695–704. doi:10.1161/CIRCRESAHA.109.206243. PMID 20044516. 
  24. ^ a b c Boateng SY, Senyo SE, Qi L, Goldspink PH, Russell B (Oct 2009). "Myocyte remodeling in response to hypertrophic stimuli requires nucleocytoplasmic shuttling of muscle LIM protein". Journal of Molecular and Cellular Cardiology. 47 (4): 426–35. doi:10.1016/j.yjmcc.2009.04.006. PMC 2739242Freely accessible. PMID 19376126. 
  25. ^ a b Clark KA, Bland JM, Beckerle MC (Jun 2007). "The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain muscle structural integrity". Journal of Cell Science. 120 (Pt 12): 2066–77. doi:10.1242/jcs.000695. PMID 17535853. 
  26. ^ Clark KA, Kadrmas JL (Jun 2013). "Drosophila melanogaster muscle LIM protein and alpha-actinin function together to stabilize muscle cytoarchitecture: a potential role for Mlp84B in actin-crosslinking". Cytoskeleton. 70 (6): 304–16. doi:10.1002/cm.21106. PMC 3716849Freely accessible. PMID 23606669. 
  27. ^ Arber S, Caroni P (Feb 1996). "Specificity of single LIM motifs in targeting and LIM/LIM interactions in situ". Genes & Development. 10 (3): 289–300. doi:10.1101/gad.10.3.289. PMID 8595880. 
  28. ^ a b c Arber S, Hunter JJ, Ross J, Hongo M, Sansig G, Borg J, Perriard JC, Chien KR, Caroni P (Feb 1997). "MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure". Cell. 88 (3): 393–403. doi:10.1016/s0092-8674(00)81878-4. PMID 9039266. 
  29. ^ Frank D, Frey N (Mar 2011). "Cardiac Z-disc signaling network". The Journal of Biological Chemistry. 286 (12): 9897–904. doi:10.1074/jbc.R110.174268. PMC 3060542Freely accessible. PMID 21257757. 
  30. ^ Gautel M (Feb 2011). "The sarcomeric cytoskeleton: who picks up the strain?". Current Opinion in Cell Biology. 23 (1): 39–46. doi:10.1016/j.ceb.2010.12.001. PMID 21190822. 
  31. ^ Luther PK (2009). "The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling". Journal of Muscle Research and Cell Motility. 30 (5–6): 171–85. doi:10.1007/s10974-009-9189-6. PMC 2799012Freely accessible. PMID 19830582. 
  32. ^ Buyandelger B, Ng KE, Miocic S, Gunkel S, Piotrowska I, Ku CH, Knöll R (Jun 2011). "Genetics of mechanosensation in the heart". Journal of Cardiovascular Translational Research. 4 (3): 238–44. doi:10.1007/s12265-011-9262-6. PMC 3098994Freely accessible. PMID 21360311. 
  33. ^ Hoffmann C, Moreau F, Moes M, Luthold C, Dieterle M, Goretti E, Neumann K, Steinmetz A, Thomas C (Aug 2014). "Human muscle LIM protein dimerizes along the actin cytoskeleton and cross-links actin filaments". Molecular and Cellular Biology. 34 (16): 3053–65. doi:10.1128/MCB.00651-14. PMC 4135597Freely accessible. PMID 24934443. 
  34. ^ a b c Esposito G, Santana LF, Dilly K, Cruz JD, Mao L, Lederer WJ, Rockman HA (Dec 2000). "Cellular and functional defects in a mouse model of heart failure". American Journal of Physiology. Heart and Circulatory Physiology. 279 (6): H3101–12. PMID 11087268. 
  35. ^ a b Kemecsei P, Miklós Z, Bíró T, Marincsák R, Tóth BI, Komlódi-Pásztor E, Barnucz E, Mirk E, Van der Vusse GJ, Ligeti L, Ivanics T (Sep 2010). "Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling". Molecular and Cellular Biochemistry. 342 (1–2): 251–60. doi:10.1007/s11010-010-0492-8. PMID 20490897. 
  36. ^ a b c Su Z, Yao A, Zubair I, Sugishita K, Ritter M, Li F, Hunter JJ, Chien KR, Barry WH (Jun 2001). "Effects of deletion of muscle LIM protein on myocyte function". American Journal of Physiology. Heart and Circulatory Physiology. 280 (6): H2665–73. PMID 11356623. 
  37. ^ van den Bosch BJ, van den Burg CM, Schoonderwoerd K, Lindsey PJ, Scholte HR, de Coo RF, van Rooij E, Rockman HA, Doevendans PA, Smeets HJ (Feb 2005). "Regional absence of mitochondria causing energy depletion in the myocardium of muscle LIM protein knockout mice". Cardiovascular Research. 65 (2): 411–8. doi:10.1016/j.cardiores.2004.10.025. PMID 15639480. 
  38. ^ a b Geier C, Gehmlich K, Ehler E, Hassfeld S, Perrot A, Hayess K, Cardim N, Wenzel K, Erdmann B, Krackhardt F, Posch MG, Osterziel KJ, Bublak A, Nägele H, Scheffold T, Dietz R, Chien KR, Spuler S, Fürst DO, Nürnberg P, Ozcelik C (Sep 2008). "Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy". Human Molecular Genetics. 17 (18): 2753–65. doi:10.1093/hmg/ddn160. PMID 18505755. 
  39. ^ Geier C, Perrot A, Ozcelik C, Binner P, Counsell D, Hoffmann K, Pilz B, Martiniak Y, Gehmlich K, van der Ven PF, Fürst DO, Vornwald A, von Hodenberg E, Nürnberg P, Scheffold T, Dietz R, Osterziel KJ (Mar 2003). "Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy". Circulation. 107 (10): 1390–5. doi:10.1161/01.cir.0000056522.82563.5f. PMID 12642359. 
  40. ^ Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S, Jakobs P, Nauman D, Burgess D, Partain J, Litt M (May 2008). "Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy". Clinical and Translational Science. 1 (1): 21–6. doi:10.1111/j.1752-8062.2008.00017.x. PMC 2633921Freely accessible. PMID 19412328. 
  41. ^ a b Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG, Chrisco MA, Murphy RT, Lurie PR, Schwartz RJ, Elliott PM, Vatta M, McKenna W, Towbin JA, Bowles NE (2002). "Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis". Molecular Genetics and Metabolism. 80 (1–2): 207–15. doi:10.1016/s1096-7192(03)00142-2. PMID 14567970. 
  42. ^ Sanoudou D, Corbett MA, Han M, Ghoddusi M, Nguyen MA, Vlahovich N, Hardeman EC, Beggs AH (Sep 2006). "Skeletal muscle repair in a mouse model of nemaline myopathy". Human Molecular Genetics. 15 (17): 2603–12. doi:10.1093/hmg/ddl186. PMC 3372923Freely accessible. PMID 16877500. 
  43. ^ von der Hagen M, Laval SH, Cree LM, Haldane F, Pocock M, Wappler I, Peters H, Reitsamer HA, Hoger H, Wiedner M, Oberndorfer F, Anderson LV, Straub V, Bittner RE, Bushby KM (Dec 2005). "The differential gene expression profiles of proximal and distal muscle groups are altered in pre-pathological dysferlin-deficient mice". Neuromuscular Disorders. 15 (12): 863–77. doi:10.1016/j.nmd.2005.09.002. PMID 16288871. 
  44. ^ Winokur ST, Chen YW, Masny PS, Martin JH, Ehmsen JT, Tapscott SJ, van der Maarel SM, Hayashi Y, Flanigan KM (Nov 2003). "Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation". Human Molecular Genetics. 12 (22): 2895–907. doi:10.1093/hmg/ddg327. PMID 14519683. 
  45. ^ Omens JH, Usyk TP, Li Z, McCulloch AD (Feb 2002). "Muscle LIM protein deficiency leads to alterations in passive ventricular mechanics". American Journal of Physiology. Heart and Circulatory Physiology. 282 (2): H680–7. doi:10.1152/ajpheart.00773.2001. PMID 11788418. 
  46. ^ Wilson AJ, Schoenauer R, Ehler E, Agarkova I, Bennett PM (Jan 2014). "Cardiomyocyte growth and sarcomerogenesis at the intercalated disc". Cellular and Molecular Life Sciences. 71 (1): 165–81. doi:10.1007/s00018-013-1374-5. PMC 3889684Freely accessible. PMID 23708682. 
  47. ^ a b Fajardo G, Zhao M, Urashima T, Farahani S, Hu DQ, Reddy S, Bernstein D (Oct 2013). "Deletion of the β2-adrenergic receptor prevents the development of cardiomyopathy in mice". Journal of Molecular and Cellular Cardiology. 63: 155–64. doi:10.1016/j.yjmcc.2013.07.016. PMC 3791213Freely accessible. PMID 23920331. 
  48. ^ a b Heineke J, Wollert KC, Osinska H, Sargent MA, York AJ, Robbins J, Molkentin JD (Jun 2010). "Calcineurin protects the heart in a murine model of dilated cardiomyopathy". Journal of Molecular and Cellular Cardiology. 48 (6): 1080–7. doi:10.1016/j.yjmcc.2009.10.012. PMC 2891089Freely accessible. PMID 19854199. 
  49. ^ Minamisawa S, Hoshijima M, Chu G, Ward CA, Frank K, Gu Y, Martone ME, Wang Y, Ross J, Kranias EG, Giles WR, Chien KR (Oct 1999). "Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy". Cell. 99 (3): 313–22. doi:10.1016/s0092-8674(00)81662-1. PMID 10555147. 
  50. ^ Rockman HA, Chien KR, Choi DJ, Iaccarino G, Hunter JJ, Ross J, Lefkowitz RJ, Koch WJ (Jun 1998). "Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice". Proceedings of the National Academy of Sciences of the United States of America. 95 (12): 7000–5. doi:10.1073/pnas.95.12.7000. PMC 22717Freely accessible. PMID 9618528. 
  51. ^ Yamamoto R, Akazawa H, Ito K, Toko H, Sano M, Yasuda N, Qin Y, Kudo Y, Sugaya T, Chien KR, Komuro I (Dec 2007). "Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice". Circulation Journal. 71 (12): 1958–64. doi:10.1253/circj.71.1958. PMID 18037754. 
  52. ^ Clark KA, Lesage-Horton H, Zhao C, Beckerle MC, Swank DM (Aug 2011). "Deletion of Drosophila muscle LIM protein decreases flight muscle stiffness and power generation". American Journal of Physiology. Cell Physiology. 301 (2): C373–82. doi:10.1152/ajpcell.00206.2010. PMC 3154547Freely accessible. PMID 21562304. 
  53. ^ Mery A, Taghli-Lamallem O, Clark KA, Beckerle MC, Wu X, Ocorr K, Bodmer R (Jan 2008). "The Drosophila muscle LIM protein, Mlp84B, is essential for cardiac function". The Journal of Experimental Biology. 211 (Pt 1): 15–23. doi:10.1242/jeb.012435. PMID 18083727. 

External links[edit]