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Review
. 2010:2010:652065.
doi: 10.1155/2010/652065. Epub 2010 Apr 8.

Myosin binding protein-C slow: an intricate subfamily of proteins

Maegen A Ackermann  1 , Aikaterini Kontrogianni-Konstantopoulos
Affiliations
Review

Myosin binding protein-C slow: an intricate subfamily of proteins

Maegen A Ackermann et al. J Biomed Biotechnol. 2010.

Abstract

Myosin binding protein C (MyBP-C) consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal, and fast skeletal. To date, most studies have focused on the cardiac form, due to its direct involvement in the development of hypertrophic cardiomyopathy. Here we focus on the slow skeletal form, discuss past and current literature, and present evidence to support that: (i) MyBP-C slow comprises a subfamily of four proteins, resulting from complex alternative shuffling of the single MyBP-C slow gene, (ii) the four MyBP-C slow isoforms are expressed in variable amounts in different skeletal muscles, (iii) at least one MyBP-C slow isoform is preferentially found at the periphery of M-bands and (iv) the MyBP-C slow subfamily may play important roles in the assembly and stabilization of sarcomeric M- and A-bands and regulate the contractile properties of the actomyosin filaments.

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Figures

Figure 1
Figure 1
(a): Schematic representation of MyBP-C slow variants 1–4, showing their common structural motifs and novel insertions; white and grey ovals represent Ig and FN-III domains, respectively, while green, yellow, and red rectangles correspond to the NH2-terminal, Ig7, and COOH-terminal inserts, respectively. The NH2-terminal insert is present in variants 1 and 2, while the Ig7 and COOH-terminal inserts are present in variants 3 and 1, respectively. Variant 4 does not contain any of the three inserts. (b–d): Complex alternative splicing events result in the inclusion of exons 3 and 4, exon 23 and exon 31 that encode the NH2-terminal (b), Ig7 (c), and COOH-terminal (d) novel insertions. The amino acid and nucleotide compositions of the three insertions are shown.
Figure 2
Figure 2
RT-PCR analysis using cDNA generated from developing and adult rat extensor digitorum longus (EDL), flexor digitorum brevis (FDB), tibialis anterior (TA), gastrocnemius (gastroc), quadriceps (quad) and soleus skeletal muscles and primer sets designed to flank the NH2-terminal (a), Ig7 (b), and COOH-terminal (c) insertions. A schematic representation of the amplified region is shown in the upper left corner of each panel. White and grey ovals depict Ig and FN-III domains, respectively, while the 3′ UTR is shown as a black line. The zig-zag lines denote the three novel insertions. In each amplification reaction, the top band corresponds to transcripts that include the insertion of interest, whereas the bottom band corresponds to transcripts that lack it. (a): All skeletal muscles tested contain a mixed population of MyBP-C slow variants that contain and lack the NH2-terminal insertion, as indicated by the presence of two amplification products. (b): On the contrary, only soleus and developing myotubes express transcripts that include the Ig7 insertion. (c): With the exception of quadriceps muscle that only contains MyBP-C slow variants that lack the COOH-terminal insertion, all other muscles examined contain a mixed pool of transcripts that carry and lack the novel COOH-terminal insertion.
Figure 3
Figure 3
Western blot analysis of protein homogenates prepared from rat skeletal muscles and blotted with antibodies to the fifth Ig domain that recognize all MyBP-C slow variants (a) or to the novel COOH-terminal insertion that specifically recognizes variant 1 (b). (a) Top panel: With the exception of quadriceps, all other muscles express variant 1, represented by the upper most band, marked by a blue dot. All adult skeletal muscles tested, but not the developing myofibers, express variants 2 and/or 3, corresponding to the band with the intermediate mobility, and denoted with a red dot. As variants 2 and 3 have similar molecular weights (129 and 128 kDa, respectively), it is not feasible to separate them in the current gel system. Moreover, variant 4 is detected in homogenates prepared from EDL, FDB, gastrocnemious, and soleus, and is represented by the lower immunoreactive band, marked with a green dot. Bottom panel: A cartoon showing the presence of the different MyBP-C slow variants in developing and adult skeletal muscles. Dotted lines correspond to immunoreactive bands, which are evident only after long exposure times. (b) In agreement with the immunoblot shown in panel (a), antibodies specific for the novel COOH-terminal insert demonstrated that EDL, FDB, TA, gastrocnemious, soleus, and P1 skeletal myotubes express variant 1, with soleus containing the highest amounts.
Figure 4
Figure 4
Ultrathin cryo-sections of adult mouse FDB skeletal muscle were labeled with antibodies specific for the COOH-terminal insertion present in MyBP-C slow variant 1. (a) Variant 1 was detected at the periphery of the M-band (arrows). The boxed area in (a) is blown up in (b) for ease of visualization of the immunolabeling. Scale bar corresponds to 0.5 μm.
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References

    1. Clark KA, McElhinny AS, Beckerle MC, Gregorio CC. Striated muscle cytoarchitecture: an intricate web of form and function. Annual Review of Cell and Developmental Biology. 2002;18:637–706. - PubMed
    1. Franzini-Armstrong C. Functional significance of membrane architecture in skeletal and cardiac muscle. Society of General Physiologists series. 1996;51:3–18. - PubMed
    1. Oakley CE, Chamoun J, Brown LJ, Hambly BD. Myosin binding protein-C: enigmatic regulator of cardiac contraction. International Journal of Biochemistry and Cell Biology. 2007;39(12):2161–2166. - PubMed
    1. Starr R, Offer G. Polypeptide chains of intermediate molecular weight in myosin preparations. FEBS Letters. 1971;15(1):40–44. - PubMed
    1. Hartzell HC, Sale WS. Structure of C protein purified from cardiac muscle. Journal of Cell Biology. 1985;100(1):208–215. - PMC - PubMed

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