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.
Structure
Nebulette is a 116.4 kDa protein composed of 1014 amino acids.[3][4] 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.[5] 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.[6] 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).[7] Nebulette interacts with
actin,
tropomyosin,
alpha-actinin.[8]Xin, and
XIRP2.[9]
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.[10] Normal expression of nebulette is essential for the assembly and
contractile function of
myofibrils.[11] 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.[12][13]
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton. 32 (3): 205–25.
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): 205–25.
doi:
10.1002/cm.970320305.
PMID8581976.
^Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research. 273 (2): 204–18.
doi:
10.1006/excr.2001.5423.
PMID11822876.
^Bonzo JR, Norris AA, Esham M, Moncman CL (Nov 2008). "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere". Experimental Cell Research. 314 (19): 3519–30.
doi:
10.1016/j.yexcr.2008.09.001.
PMID18823973.
^Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research. 273 (2): 204–18.
doi:
10.1006/excr.2001.5423.
PMID11822876.
^Arimura T, Nakamura T, Hiroi S, Satoh M, Takahashi M, Ohbuchi N, Ueda K, Nouchi T, Yamaguchi N, Akai J, Matsumori A, Sasayama S, Kimura A (Nov 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): 440–51.
doi:
10.1007/s004390000389.
PMID11140941.
S2CID4564490.
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.
Structure
Nebulette is a 116.4 kDa protein composed of 1014 amino acids.[3][4] 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.[5] 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.[6] 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).[7] Nebulette interacts with
actin,
tropomyosin,
alpha-actinin.[8]Xin, and
XIRP2.[9]
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.[10] Normal expression of nebulette is essential for the assembly and
contractile function of
myofibrils.[11] 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.[12][13]
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton. 32 (3): 205–25.
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): 205–25.
doi:
10.1002/cm.970320305.
PMID8581976.
^Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research. 273 (2): 204–18.
doi:
10.1006/excr.2001.5423.
PMID11822876.
^Bonzo JR, Norris AA, Esham M, Moncman CL (Nov 2008). "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere". Experimental Cell Research. 314 (19): 3519–30.
doi:
10.1016/j.yexcr.2008.09.001.
PMID18823973.
^Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research. 273 (2): 204–18.
doi:
10.1006/excr.2001.5423.
PMID11822876.
^Arimura T, Nakamura T, Hiroi S, Satoh M, Takahashi M, Ohbuchi N, Ueda K, Nouchi T, Yamaguchi N, Akai J, Matsumori A, Sasayama S, Kimura A (Nov 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): 440–51.
doi:
10.1007/s004390000389.
PMID11140941.
S2CID4564490.