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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/03 20:01:33」(JST)

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Nebulin is an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle. It is a very large protein (600-900 kDa) and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during sarcomere assembly.^[2] Other functions of nebulin, such as a role in cell signaling, remain uncertain.

Nebulin has also been shown to regulate actin-myosin interactions by inhibiting ATPase activity in a calcium-calmodulin sensitive manner.^[3]

Mutations in nebulin cause some cases of the autosomal recessive disorder nemaline myopathy.^[4]

A smaller member of the nebulin protein family termed nebulette, is expressed in cardiac muscle.

Structure

The structure of the SH3 domain of nebulin was determined by NMR.^[1] The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the beta sheet secondary structure (7 strands; 18 residues).

Knockout phenotype

As of 2007, two knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues^[5] demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of myofibrils. Witt and colleagues^[6] had similar results in their mice, which also died postnatally with reduced thin filament length and contractile function. These nebulin-knockout mice are being investigated as animal models of nemaline myopathy.

References

^ ^a ^b PDB: 1NEB ; Politou AS, Millevoi S, Gautel M, Kolmerer B, Pastore A (February 1998). "SH3 in muscles: solution structure of the SH3 domain from nebulin". J. Mol. Biol. 276 (1): 189–202. doi:10.1006/jmbi.1997.1521. PMID 9514727.
^ McElhinny AS, Kazmierski ST, Labeit S, Gregorio CC (Jul 2003). "Nebulin: the nebulous, multifunctional giant of striated muscle". Trends in Cardiovascular Medicine 13 (5): 195–201. doi:10.1016/S1050-1738(03)00076-8. PMID 12837582.
^ Root DD, Wang K (Oct 1994). "Calmodulin-sensitive interaction of human nebulin fragments with actin and myosin". Biochemistry 33 (42): 12581–91. doi:10.1021/bi00208a008. PMID 7918483.
^ Pelin K, Hilpelä P, Donner K, Sewry C, Akkari PA, Wilton SD, Wattanasirichaigoon D, Bang ML, Centner T, Hanefeld F, Odent S, Fardeau M, Urtizberea JA, Muntoni F, Dubowitz V, Beggs AH, Laing NG, Labeit S, de la Chapelle A, Wallgren-Pettersson C (Mar 1999). "Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy". Proceedings of the National Academy of Sciences of the United States of America 96 (5): 2305–10. doi:10.1073/pnas.96.5.2305. PMC 26779. PMID 10051637.
^ Bang ML, Li X, Littlefield R, Bremner S, Thor A, Knowlton KU, Lieber RL, Chen J (Jun 2006). "Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle". The Journal of Cell Biology 173 (6): 905–16. doi:10.1083/jcb.200603119. PMC 2063916. PMID 16769824.
^ Witt CC, Burkart C, Labeit D, McNabb M, Wu Y, Granzier H, Labeit S (Aug 2006). "Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo". The EMBO Journal 25 (16): 3843–55. doi:10.1038/sj.emboj.7601242. PMC 1553189. PMID 16902413.

External links

nebulin at the US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy

UpToDate Contents

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Evidence of peptide oxidation from major myofibrillar proteins in dry-cured ham.

Gallego M1, Mora L1, Aristoy MC1, Toldrá F2.
Food chemistry.Food Chem.2015 Nov 15;187:230-5. doi: 10.1016/j.foodchem.2015.04.102. Epub 2015 Apr 23.
In this study, a peptidomic approach has been used in the identification of naturally generated peptides during a dry-curing process, showing methionine (Met) oxidation in their sequence. A total of 656 peptides derived from major myofibrillar proteins in Protected Designation of Origin (PDO) Teruel
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Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy.

Li F1, Buck D1, De Winter J2, Kolb J1, Meng H3, Birch C4, Slater R1, Escobar YN1, Smith JE 3rd1, Yang L5, Konhilas J4, Lawlor MW3, Ottenheijm C6, Granzier HL7.
Human molecular genetics.Hum Mol Genet.2015 Sep 15;24(18):5219-33. doi: 10.1093/hmg/ddv243. Epub 2015 Jun 29.
Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere. Nebulin mutations are the main cause of nemaline myopathy (NEM), with typical adult patients having low expression of nebulin, yet the roles of nebulin in adult muscle remain poorly
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Zebrafish models for nemaline myopathy reveal a spectrum of nemaline bodies contributing to reduced muscle function.

Sztal TE1, Zhao M, Williams C, Oorschot V, Parslow AC, Giousoh A, Yuen M, Hall TE, Costin A, Ramm G, Bird PI, Busch-Nentwich EM, Stemple DL, Currie PD, Cooper ST, Laing NG, Nowak KJ, Bryson-Richardson RJ.
Acta neuropathologica.Acta Neuropathol.2015 Sep;130(3):389-406. doi: 10.1007/s00401-015-1430-3. Epub 2015 May 1.
Nemaline myopathy is characterized by muscle weakness and the presence of rod-like (nemaline) bodies. The genetic etiology of nemaline myopathy is becoming increasingly understood with mutations in ten genes now known to cause the disease. Despite this, the mechanism by which skeletal muscle weaknes
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Japanese Journal

Meat Tenderizing Effect of Injecting Encapsulated Ca〔2+〕 in Liposome into Rabbit before Slaughter

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… SDS–PAGE patterns of connectin and nebulin show that the total degradation of connectin by the control group took longer than 2–3 days, while it was within 1 day for the L-Ca-injected group. … The control group took 8–10 days for nebulin, while the L-Ca-injected group took 2–3 days for total degradation. …
NAID 130000030117

C-TERMINAL REGION OF NEBULIN FROM AMPHIOXUS STRIATED MUSCLE(Cell Biology and Morphology,Abstracts of papers presented at the 76^<th>

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Related Pictures

★リンクテーブル★

リンク元	「ネブリン」「nephrin」

「ネブリン」

Nebulin
	Solution structure of the SH3 domain from human nebulin.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1ARK, 1NEB
Identifiers
Symbols	NEB ; NEB177D; NEM2
External IDs	OMIM: 161650 HomoloGene: 136285 GeneCards: NEB Gene
Gene ontology
Molecular function	• actin binding; • protein binding; • structural constituent of muscle;
Cellular component	• cytosol; • actin cytoskeleton; • Z disc; • extracellular vesicular exosome;
Biological process	• muscle organ development; • somatic muscle development; • muscle filament sliding; • regulation of actin filament length;
	Sources: Amigo / QuickGO
Orthologs
	v; t; e;