Biology:Nebulette

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.

Structure

Nebulette is a 116.4 kDa protein composed of 1014 amino acids.[1][2] As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved SDxxYK motif.[3] Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to an SH3 domain at its C-terminus.[4] Though nebulette shares structural features with nebulin, nebulin is expressed preferentially in skeletal muscle and has an enormous size (600-900 kDa), while nebulette is expressed in cardiac muscle at Z-disc regions and is significantly smaller (roughly 1/6 of the size).[5] Nebulette interacts with actin, tropomyosin, alpha-actinin.[6] Xin, and XIRP2.[7]

Function

Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic cardiomyocytes by immunoprecipitations with certain anti-nebulin monoclonal antibodies.[8] Normal expression of nebulette is essential for the assembly and contractile function of myofibrils.[9] Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteins troponin I and tropomyosin.[10][11]

Clinical significance

Mutations in the NEBL gene have been associated with dilated cardiomyopathy.[12] Studies in transgenic mice have supported their causative role in endocardial fibroelastosis and dilated cardiomyopathy.[13]

Further reading

References

  1. ↑ "Nebulette". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O76041. 
  2. ↑ Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K. et al. (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  3. ↑ "Evidence that nebulin is a protein-ruler in muscle thin filaments". FEBS Letters 282 (2): 313–6. May 1991. doi:10.1016/0014-5793(91)80503-u. PMID 2037050. 
  4. ↑ "The Nebulin family: an actin support group". Trends in Cell Biology 21 (1): 29–37. Jan 2011. doi:10.1016/j.tcb.2010.09.005. PMID 20951588. 
  5. ↑ "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton 32 (3): 205–25. 1995. doi:10.1002/cm.970320305. PMID 8581976. 
  6. ↑ "Functional dissection of nebulette demonstrates actin binding of nebulin-like repeats and Z-line targeting of SH3 and linker domains". Cell Motility and the Cytoskeleton 44 (1): 1–22. 1999. doi:10.1002/(SICI)1097-0169(199909)44:1<1::AID-CM1>3.0.CO;2-8. PMID 10470015. 
  7. ↑ Eulitz, S; Sauer, F; Pelissier, M. C.; Boisguerin, P; Molt, S; Schuld, J; Orfanos, Z; Kley, R. A. et al. (2013). "Identification of Xin-repeat proteins as novel ligands of the SH3 domains of nebulin and nebulette and analysis of their interaction during myofibril formation and remodeling". Molecular Biology of the Cell 24 (20): 3215–26. doi:10.1091/mbc.E13-04-0202. PMID 23985323. 
  8. ↑ "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton 32 (3): 205–25. 1995. doi:10.1002/cm.970320305. PMID 8581976. 
  9. ↑ "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research 273 (2): 204–18. Feb 2002. doi:10.1006/excr.2001.5423. PMID 11822876. 
  10. ↑ "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere". Experimental Cell Research 314 (19): 3519–30. Nov 2008. doi:10.1016/j.yexcr.2008.09.001. PMID 18823973. 
  11. ↑ "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research 273 (2): 204–18. Feb 2002. doi:10.1006/excr.2001.5423. PMID 11822876. 
  12. ↑ "Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy". Human Genetics 107 (5): 440–51. Nov 2000. doi:10.1007/s004390000389. PMID 11140941. 
  13. ↑ "Nebulette mutations are associated with dilated cardiomyopathy and endocardial fibroelastosis". Journal of the American College of Cardiology 56 (18): 1493–502. Oct 2010. doi:10.1016/j.jacc.2010.05.045. PMID 20951326. 
  14. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–1053. Oct 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 

External links



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