| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Departments of Physiology and
Anatomy and Neurobiology, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland, USA; and
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
1Correspondence: Department of Physiology, University of Maryland Baltimore, School of Medicine, Baltimore, MD 21201, USA. E-mail: akons001{at}umaryland.edu
Obscurin (
800 kDa) in striated muscle closely surrounds sarcomeres at the level of the M-band and Z-disk where, we hypothesize, it participates in the assembly of the contractile apparatus and membrane systems required for Ca2+ homeostasis. In this study, we used small inhibitory RNA (siRNA) technology to reduce the levels of obscurin in primary cultures of skeletal myotubes to study its role in myofibrillogenesis and the organization of the sarcoplasmic reticulum (SR). siRNA-treated myotubes showed a specific and dramatic reduction in the 800 kDa form of obscurin by reverse transcription-polymerase chain reaction, immunoblotting, and immunofluorescence. M-bands and A-bands, but not Z-disks or I-bands, were disrupted when the synthesis of obscurin was inhibited. Small ankyrin 1, an integral protein of the network SR that binds to obscurin, also failed to align around developing sarcomeres in treated myotubes. Myosin and myomesin levels were significantly reduced in treated myotubes but 
-actinin was not, suggesting that down-regulation of obscurin destabilizes proteins of the M-band and A-band but not of the Z-disk. Our findings suggest that obscurin is required for the assembly of the M-band and A-band and for the regular alignment of the network SR around the contractile apparatus.—Kontrogianni-Konstantopoulos, A., Catino, D. H., Strong, J. C., Sutter, S., Borisov, A. B., Pumplin, D. W., Russell, M. W., Bloch, R. J. Obscurin modulates the assembly and organization of sarcomeres and the sarcoplasmic reticulum.
Key Words: obscurin • myosin • myomesin • titin • small ankyrin 1 • A-band • M-band
This article has been cited by other articles:
|
|
 |
|
  M. A. Ackermann, L.-Y. R. Hu, A. L. Bowman, R. J. Bloch, and A. Kontrogianni-Konstantopoulos Obscurin Interacts with a Novel Isoform of MyBP-C Slow at the Periphery of the Sarcomeric M-Band and Regulates Thick Filament Assembly Mol. Biol. Cell, June 15, 2009; 20(12): 2963 - 2978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Coisy-Quivy, O. Touzet, A. Bourret, R. A. Hipskind, J. Mercier, P. Fort, and A. Philips TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin J. Cell Sci., April 1, 2009; 122(7): 947 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Cusimano, F. Pampinella, E. Giacomello, and V. Sorrentino Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells PNAS, March 24, 2009; 106(12): 4695 - 4700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Cunha and P. J. Mohler Obscurin Targets Ankyrin-B and Protein Phosphatase 2A to the Cardiac M-line J. Biol. Chem., November 14, 2008; 283(46): 31968 - 31980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Bowman, D. H. Catino, J. C. Strong, W. R. Randall, A. Kontrogianni-Konstantopoulos, and R. J. Bloch The Rho-Guanine Nucleotide Exchange Factor Domain of Obscurin Regulates Assembly of Titin at the Z-Disk through Interactions with Ran Binding Protein 9 Mol. Biol. Cell, September 1, 2008; 19(9): 3782 - 3792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fukuzawa, S. Lange, M. Holt, A. Vihola, V. Carmignac, A. Ferreiro, B. Udd, and M. Gautel Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band - implications for hereditary myopathies J. Cell Sci., June 1, 2008; 121(11): 1841 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. R. Healy, F. Zhu, J. D. Stull, and K. Konstantopoulos Elucidation of the signaling network of COX-2 induction in sheared chondrocytes: COX-2 is induced via a Rac/MEKK1/MKK7/JNK2/c-Jun-C/EBP{beta}-dependent pathway Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1146 - C1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Lowe, O. Palygin, N. Bhasin, T. J. Hund, P. A. Boyden, E. Shibata, M. E. Anderson, and P. J. Mohler Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway J. Cell Biol., January 10, 2008; 180(1): 173 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Borzok, D. H. Catino, J. D. Nicholson, A. Kontrogianni-Konstantopoulos, and R. J. Bloch Mapping the Binding Site on Small Ankyrin 1 for Obscurin J. Biol. Chem., November 2, 2007; 282(44): 32384 - 32396. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
