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Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly.

Young P, Ehler E, Gautel M - J. Cell Biol. (2001)

Bottom Line: It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle.Both proteins coassemble during myofibrillogenesis.The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, Structural Biology Division, 69117 Heidelberg, Germany.

ABSTRACT
Vertebrate-striated muscle is assumed to owe its remarkable order to the molecular ruler functions of the giant modular signaling proteins, titin and nebulin. It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle. In this paper we report the identification of a third giant protein from vertebrate muscle, obscurin, encoded on chromosome 1q42. Obscurin is approximately 800 kD and is expressed specifically in skeletal and cardiac muscle. The complete cDNA sequence of obscurin reveals a modular architecture, consisting of >67 intracellular immunoglobulin (Ig)- or fibronectin-3-like domains with multiple splice variants. A large region of obscurin shows a modular architecture of tandem Ig domains reminiscent of the elastic region of titin. The COOH-terminal region of obscurin interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin. Both proteins coassemble during myofibrillogenesis. During the progression of myofibrillogenesis, all obscurin epitopes become detectable at the M band. The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere.

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Localization of endogenous obscurin (green for all antibodies) in E14.5 rat hearts. At this developmental stage, myofibrils are arranged in mature, parallel bundles and all obscurin epitopes detectable at this stage are found at the M-bands, as shown by the alternating staining pattern with Z-disk titin (T12, red; F-actin, blue). (A) α-Ob48–49; (B) α-Ob51–52; (C) α–Ob-DH. Bar, 10 μm.
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fig8: Localization of endogenous obscurin (green for all antibodies) in E14.5 rat hearts. At this developmental stage, myofibrils are arranged in mature, parallel bundles and all obscurin epitopes detectable at this stage are found at the M-bands, as shown by the alternating staining pattern with Z-disk titin (T12, red; F-actin, blue). (A) α-Ob48–49; (B) α-Ob51–52; (C) α–Ob-DH. Bar, 10 μm.

Mentions: Localization of endogenous obscurin in developing hearts demonstrates a relocalization of epitopes during development. Hearts of embryonic chicken (A–D) or mouse (E) are stained with antibodies raised against various obscurin epitopes (green). The titin Z-disk epitope T-12 is stained in red and the actin cytoskeleton in blue. The resulting color of titin and obscurin colocalization is yellow to bluish white here and in Fig. 8, depending on the background of blue actin staining. (A) Chick, 8-somite stage: the α-Ob48–49 epitope colocalizes with titin T12 in dots or cross-striated patterns on actin-filaments at the cell periphery (arrows). (B) Chick, 10-somite stage: α-Ob48–49 is predominantly colocalized with titin T12 at the Z-disk (arrows). (C) and (D) Chick, 10-somite stage: the α-Ob51–52 and α–Ob-DH epitopes, respectively, are diffusely localized or partly detected at the M-band (arrowheads in D). M-band localization is observed in myofibrils with parallel arrangements but unaligned myofibrils show diffuse localization (arrows in D). (E) Mouse (E9.5) relocalization of the α-Ob48–49 epitope is observed which shows prominent M-band and weaker Z-disk staining with α-Ob48–49. Note that the myofibrils in these hearts begin to align in parallel compared with the criss-cross patterns observed in early chicken hearts. Bar, 4 μm.


Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly.

Young P, Ehler E, Gautel M - J. Cell Biol. (2001)

Localization of endogenous obscurin (green for all antibodies) in E14.5 rat hearts. At this developmental stage, myofibrils are arranged in mature, parallel bundles and all obscurin epitopes detectable at this stage are found at the M-bands, as shown by the alternating staining pattern with Z-disk titin (T12, red; F-actin, blue). (A) α-Ob48–49; (B) α-Ob51–52; (C) α–Ob-DH. Bar, 10 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196875&req=5

fig8: Localization of endogenous obscurin (green for all antibodies) in E14.5 rat hearts. At this developmental stage, myofibrils are arranged in mature, parallel bundles and all obscurin epitopes detectable at this stage are found at the M-bands, as shown by the alternating staining pattern with Z-disk titin (T12, red; F-actin, blue). (A) α-Ob48–49; (B) α-Ob51–52; (C) α–Ob-DH. Bar, 10 μm.
Mentions: Localization of endogenous obscurin in developing hearts demonstrates a relocalization of epitopes during development. Hearts of embryonic chicken (A–D) or mouse (E) are stained with antibodies raised against various obscurin epitopes (green). The titin Z-disk epitope T-12 is stained in red and the actin cytoskeleton in blue. The resulting color of titin and obscurin colocalization is yellow to bluish white here and in Fig. 8, depending on the background of blue actin staining. (A) Chick, 8-somite stage: the α-Ob48–49 epitope colocalizes with titin T12 in dots or cross-striated patterns on actin-filaments at the cell periphery (arrows). (B) Chick, 10-somite stage: α-Ob48–49 is predominantly colocalized with titin T12 at the Z-disk (arrows). (C) and (D) Chick, 10-somite stage: the α-Ob51–52 and α–Ob-DH epitopes, respectively, are diffusely localized or partly detected at the M-band (arrowheads in D). M-band localization is observed in myofibrils with parallel arrangements but unaligned myofibrils show diffuse localization (arrows in D). (E) Mouse (E9.5) relocalization of the α-Ob48–49 epitope is observed which shows prominent M-band and weaker Z-disk staining with α-Ob48–49. Note that the myofibrils in these hearts begin to align in parallel compared with the criss-cross patterns observed in early chicken hearts. Bar, 4 μm.

Bottom Line: It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle.Both proteins coassemble during myofibrillogenesis.The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, Structural Biology Division, 69117 Heidelberg, Germany.

ABSTRACT
Vertebrate-striated muscle is assumed to owe its remarkable order to the molecular ruler functions of the giant modular signaling proteins, titin and nebulin. It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle. In this paper we report the identification of a third giant protein from vertebrate muscle, obscurin, encoded on chromosome 1q42. Obscurin is approximately 800 kD and is expressed specifically in skeletal and cardiac muscle. The complete cDNA sequence of obscurin reveals a modular architecture, consisting of >67 intracellular immunoglobulin (Ig)- or fibronectin-3-like domains with multiple splice variants. A large region of obscurin shows a modular architecture of tandem Ig domains reminiscent of the elastic region of titin. The COOH-terminal region of obscurin interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin. Both proteins coassemble during myofibrillogenesis. During the progression of myofibrillogenesis, all obscurin epitopes become detectable at the M band. The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere.

Show MeSH
Related in: MedlinePlus