HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 296/5/C1123    most recent 00503.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gokhin, D. S. Articles by Lieber, R. L. Search for Related Content PubMed PubMed Citation Articles by Gokhin, D. S. Articles by Lieber, R. L.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Reduced thin filament length in nebulin-knockout skeletal muscle alters isometric contractile properties

¹Departments of Bioengineering and Orthopaedic Surgery, University of California-San Diego, and Veterans Affairs Medical Center, La Jolla, California; ²Dulbecco Telethon Institute at Istituto Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Milan; ³Istituto di Ricovero e Cura a Carattere Scientifico Multimedica, Scientific and Technology Pole, Milan, Italy; and ⁴Department of Medicine, University of California-San Diego, La Jolla, California

Submitted 6 October 2008 ; accepted in final form 14 March 2009

Nebulin (NEB) is a large, rod-like protein believed to dictate actin thin filament length in skeletal muscle. NEB gene defects are associated with congenital nemaline myopathy. The functional role of NEB was investigated in gastrocnemius muscles from neonatal wild-type (WT) and NEB knockout (NEB-KO) mice, whose thin filaments have uniformly shorter lengths compared with WT mice. Isometric stress production in NEB-KO skeletal muscle was reduced by 27% compared with WT skeletal muscle on postnatal day 1 and by 92% on postnatal day 7, consistent with functionally severe myopathy. NEB-KO muscle was also more susceptible to a decline in stress production during a bout of 10 cyclic isometric tetani. Length-tension properties in NEB-KO muscle were altered in a manner consistent with reduced thin filament length, with length-tension curves from NEB-KO muscle demonstrating a 7.4% narrower functional range and an optimal length reduced by 0.13 muscle lengths. Expression patterns of myosin heavy chain isoforms and total myosin content did not account for the functional differences between WT and NEB-KO muscle. These data indicate that NEB is essential for active stress production, maintenance of functional integrity during cyclic activation, and length-tension properties consistent with a role in specifying normal thin filament length. Continued analysis of NEB's functional properties will strengthen the understanding of force transmission and thin filament length regulation in skeletal muscle and may provide insights into the molecular processes that give rise to nemaline myopathy.

neonatal mouse; isometric stress; myosin heavy chain; length-tension curve

This article has been cited by other articles:

				M. Chandra, R. Mamidi, S. Ford, C. Hidalgo, C. Witt, C. Ottenheijm, S. Labeit, and H. Granzier Nebulin Alters Cross-bridge Cycling Kinetics and Increases Thin Filament Activation: A NOVEL MECHANISM FOR INCREASING TENSION AND REDUCING TENSION COST J. Biol. Chem., November 6, 2009; 284(45): 30889 - 30896. [Abstract] [Full Text] [PDF]

				A. Kontrogianni-Konstantopoulos, M. A. Ackermann, A. L. Bowman, S. V. Yap, and R. J. Bloch Muscle Giants: Molecular Scaffolds in Sarcomerogenesis Physiol Rev, October 1, 2009; 89(4): 1217 - 1267. [Abstract] [Full Text] [PDF]