Nebulette is a cardiac-specific isoform belonging to the nebulin family of proteins. It is encoded by the NEBLgene. 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.
Nebulette is a 116.4 kDa protein composed of 1014 amino acids.[5][6] 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.[7] 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.[8] 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).[9] Nebulette interacts with actin, tropomyosin, alpha-actinin.[10]Xin, and XIRP2.[11]
Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic cardiomyocytes by immunoprecipitations with certain anti-nebulin monoclonal antibodies.[12] Normal expression of nebulette is essential for the assembly and contractile function of myofibrils.[13] 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.[14][15]
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton. 32 (3): 205–225. doi:10.1002/cm.970320305. PMID8581976.
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton. 32 (3): 205–225. doi:10.1002/cm.970320305. PMID8581976.
^Moncman CL, Wang K (February 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research. 273 (2): 204–218. doi:10.1006/excr.2001.5423. PMID11822876.
^Bonzo JR, Norris AA, Esham M, Moncman CL (November 2008). "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere". Experimental Cell Research. 314 (19): 3519–3530. doi:10.1016/j.yexcr.2008.09.001. PMID18823973.
^Moncman CL, Wang K (February 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research. 273 (2): 204–218. doi:10.1006/excr.2001.5423. PMID11822876.
^Arimura T, Nakamura T, Hiroi S, Satoh M, Takahashi M, Ohbuchi N, et al. (November 2000). "Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy". Human Genetics. 107 (5): 440–451. doi:10.1007/s004390000389. PMID11140941. S2CID4564490.
