A Novel Domain Sequence of Connectin Localized at the I Band of Skeletal Muscle Sarcomeres: Homology to Neurofilament Subunits

Endo, Takeshi; Kume, Hideaki; Kawamura, Yuuki; Kanzawa, Nobuyuki; Nakauchi, Yuni; Kimura, Sumiko; Kawashima, Seiichi; Maruyama, Kosçak

doi:10.1006/bbrc.1993.1963

Cited by 43 publications

(25 citation statements)

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“…How this macromolecular array of titin fibrils is organized, however, remains unclear, mainly due to a lack of information on the biochemical properties of the N2-isoforms. In the avian N2-A isoform, sequence stretches with homology to intermediate filaments were found (Maruyama et al, 1995). Furthermore, it was observed that titin epitopes near the proposed 'junction line' both in skeletal and cardiac muscle show differential movement with respect to the Z-disk and A-band (Itoh et al, 1988;Funatsu et al, 1993;TrombitAs et al, 1995).…”

Section: Introductionmentioning

confidence: 86%

Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments

Gautel

Lehtonen

Pietruschka

1996

J Muscle Res Cell Motil

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The giant molecule titin (also called connectin) provides an elastic connection in the I-band between the Z-disk and A-band of striated muscle. This region is assembled in a tissue-specific way by extensive differential splicing events. We have raised monoclonal antibodies against the two N2-line isoforms of titin and demonstrate that both forms of cardiac I-band titin are constitutively co-expressed in atrial and ventricular muscle. In developing mouse embryos, the expression of the cardiac N2-B isoform remains strictly cardiac-specific and is linked to the expression of the ubiquitous N2-A isoform. The mechanical function of the cardiac N2-line region was investigated ultrastructurally. Immunoelectron microscopy reveals that the N2-B region separates two mechanically distinct sections of titin with a hyperextensible segment spanning the distance to the Z-disk. The formation of a plateau in the extension of cardiac titin rules out that Ig-domains can be unfolded as a mechanism of elasticity.

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Section: Introductionmentioning

confidence: 86%

Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments

Gautel

Lehtonen

Pietruschka

1996

J Muscle Res Cell Motil

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“…These experiments show that the I-band region of titin contains tandem repeats of immunoglobulin-like (Ig-like) domains [46,59,81], as we|l as a region rich in proline (P), glutamate (E), valine (V), and lysine (K) residues, termed the PEVK domain [46]. Tissue-specific differences in titin are caused by alternative splicing, which leads to variations in the length of the PEVK domain as well as in the numbers of tandem Ig-like domains in the I-band region of titin [46].…”

Section: Dependence Of Passive Tension On Titin Isoformsmentioning

confidence: 98%

The physiological role of titin in striated muscle

Horowits¹

1999

Rev. Physiol. Biochem. Pharmacol.

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“…4B, anti-pK-rich antiserum gave signals at the Z-lines and at ϩ tail. Numbers in repeating motifs are arbitrarily assigned from the COOH terminus in this paper and do not match other papers (20,23). Shaded regions are the minimal binding sites to p94.…”

Section: In Pgbt9mentioning

confidence: 99%

“…Chicken sequences Ck C2-1Ј to -3Ј were taken from Ref. 23. positions between the Z-and M-lines, which are approximately 60% from the M-line toward the Z-line and roughly correspond to the N 2 -line.…”

Section: In Pgbt9mentioning

confidence: 99%

Muscle-specific Calpain, p94, Responsible for Limb Girdle Muscular Dystrophy Type 2A, Associates with Connectin through IS2, a p94-specific Sequence

Sorimachi

Kinbara

Kimura

et al. 1995

Journal of Biological Chemistry

276

231

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p94, a muscle-specific member of calpain family, is unique in that it undergoes rapid and exhaustive autolysis with a half-life of less than 1 h resulting in its disappearance from muscle. Recently, p94 was shown to be responsible for limb girdle muscular dystrophy type 2A. To elucidate the muscular proteolytic system mediated by p94 and to solve the mystery of its unusually rapid autolysis, we searched for p94-binding proteins by the two-hybrid system. Although calpain small subunit plays a crucial role for regulation of ubiquitous calpains, it did not associate with p94. After a screening of skeletal muscle library, connectin (or titin), a gigantic filamentous protein spanning the M-to Z-lines of muscle sarcomere, was found to bind to p94 through a p94-specific region, IS2. The connectin-insoluble fraction of washed myofibrils contained full-length intact p94, suggesting that connectin regulates p94 activity.Proteolysis in cytosol is a key reaction to modulate various intracellular protein functions such as signal transduction, protein turnover, and cell structure. Calpain, Ca 2ϩ -dependent cysteine proteinase (EC 3.4.22.17), is one of the major intracellular proteinases known as interacting various protein kinases, transcription factors, and cytoskeletal proteins (1-5). Ubiquitous -and m-calpains, dimers of a large catalytic (CL 1 (6) and mCL (7), respectively) and small regulatory (30K (8)) subunit. Recently, we found that the ubiquitous calpain large subunit monomer can express full proteolytic activity, and that 30K dissociates from the large subunit upon activation by Ca 2ϩ (9, 10). In other words, 30K together with calpastatin, a specific proteinaceous inhibitor for calpain, play pivotal roles in regulation of calpain activity.p94 is a muscle-specific member of the calpain large subunit family, and distinct not only from the other members but also from other proteases in that it autolyzes very rapidly and extensively leading to almost complete disappearance right after translation even in the presence of EGTA and leupeptin as observed in vitro (11,12). Ubiquitous calpains as well as many other proteases also undergo autolysis at the NH 2 terminus, but only to a limited extent. Quite recently, p94 was identified as responsible for limb girdle muscular dystrophy type 2A (LGMD2A), the first demonstration of the involvement of an enzyme in muscle dystrophy (13). To elucidate physiological meaning of this exhaustive autolysis and the molecular mechanism connecting LGMD2A and p94 function, it is important to clarify the substrates of p94 and the manner to regulate the proteolytic activity of p94.30K is the first candidate to bind to and regulate p94, since the calmodulin-like Ca 2ϩ -binding domains of CL and mCL (see Fig. 2), which are the binding sites for 30K, are highly homologous to p94 (5). Analysis of p94 at the protein level, however, is very difficult because of the extremely rapid autolysis, and, thus, we examined using the yeast two-hybrid system (14). As a result, 30K was revealed not to bind to p94...

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A Novel Domain Sequence of Connectin Localized at the I Band of Skeletal Muscle Sarcomeres: Homology to Neurofilament Subunits

Cited by 43 publications

References 0 publications

Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments

Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments

The physiological role of titin in striated muscle

Muscle-specific Calpain, p94, Responsible for Limb Girdle Muscular Dystrophy Type 2A, Associates with Connectin through IS2, a p94-specific Sequence

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