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

J. Biol. Chem., Vol. 281, Issue 35, 25768-25780, September 1, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/35/25768    most recent M513511200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lammerding, J. Articles by Lee, R. T. Search for Related Content PubMed PubMed Citation Articles by Lammerding, J. Articles by Lee, R. T. Social Bookmarking                      What's this?

Lamins A and C but Not Lamin B1 Regulate Nuclear Mechanics^*

Jan Lammerding, Recipient of a postdoctoral fellowship from the American Heart Association¹, Loren G. Fong, Julie Y. Ji, Karen Reue^¶, Colin L. Stewart^||, Stephen G. Young, and Richard T. Lee

From the Cardiovascular Division, Department of Medicine, and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02139, the Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, and the ^¶Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, and the ^||Cancer and Developmental Biology Laboratory, NCI-Frederick, Frederick, Maryland 21702

Mutations in the nuclear envelope proteins lamins A and C cause a broad variety of human diseases, including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. Cells lacking lamins A and C have reduced nuclear stiffness and increased nuclear fragility, leading to increased cell death under mechanical strain and suggesting a potential mechanism for disease. Here, we investigated the contribution of major lamin subtypes (lamins A, C, and B1) to nuclear mechanics by analyzing nuclear shape, nuclear dynamics over time, nuclear deformations under strain, and cell viability under prolonged mechanical stimulation in cells lacking both lamins A and C, cells lacking only lamin A (i.e. "lamin C-only" cells), cells lacking wild-type lamin B1, and wild-type cells. Lamin A/C-deficient cells exhibited increased numbers of misshapen nuclei and had severely reduced nuclear stiffness and decreased cell viability under strain. Lamin C-only cells had slightly abnormal nuclear shape and mildly reduced nuclear stiffness but no decrease in cell viability under strain. Interestingly, lamin B1-deficient cells exhibited normal nuclear mechanics despite having a significantly increased frequency of nuclear blebs. Our study indicates that lamins A and C are important contributors to the mechanical stiffness of nuclei, whereas lamin B1 contributes to nuclear integrity but not stiffness.

Received for publication, December 19, 2005 , and in revised form, June 7, 2006.

^* This work was supported in part by Grants HL073809, HL64858, CA099506, AR050200, and AI05438 from the National Institutes of Health and by grants from the Progeria Research Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-3, Table 1, and Videos 1-4.

¹ To whom correspondence should be addressed: Partners Research Facility, Rm. 283, 65 Landsdowne St., Cambridge, MA 02139. Tel.: 617-768-8273; Fax: 617-768-8280; E-mail: jlammerding{at}rics.bwh.harvard.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Shimi, K. Pfleghaar, S.-i. Kojima, C.-G. Pack, I. Solovei, A. E. Goldman, S. A. Adam, D. K. Shumaker, M. Kinjo, T. Cremer, et al. The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription Genes & Dev., December 15, 2008; 22(24): 3409 - 3421. [Abstract] [Full Text] [PDF]

				B. A. Kudlow, M. N. Stanfel, C. R. Burtner, E. D. Johnston, and B. K. Kennedy Suppression of Proliferative Defects Associated with Processing-defective Lamin A Mutants by hTERT or Inactivation of p53 Mol. Biol. Cell, December 1, 2008; 19(12): 5238 - 5248. [Abstract] [Full Text] [PDF]

				F. Mou, E. G. Wills, R. Park, and J. D. Baines Effects of Lamin A/C, Lamin B1, and Viral US3 Kinase Activity on Viral Infectivity, Virion Egress, and the Targeting of Herpes Simplex Virus UL34-Encoded Protein to the Inner Nuclear Membrane J. Virol., August 15, 2008; 82(16): 8094 - 8104. [Abstract] [Full Text] [PDF]

				J. M. Holaska Emerin and the Nuclear Lamina in Muscle and Cardiac Disease Circ. Res., July 3, 2008; 103(1): 16 - 23. [Abstract] [Full Text] [PDF]

				K. N. Dahl, A. J.S. Ribeiro, and J. Lammerding Nuclear Shape, Mechanics, and Mechanotransduction Circ. Res., June 6, 2008; 102(11): 1307 - 1318. [Abstract] [Full Text] [PDF]

				C. W. Tang, A. Maya-Mendoza, C. Martin, K. Zeng, S. Chen, D. Feret, S. A. Wilson, and D. A. Jackson The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells J. Cell Sci., April 1, 2008; 121(7): 1014 - 1024. [Abstract] [Full Text] [PDF]

				S. H. Yang, X. Qiao, E. Farber, S. Y. Chang, L. G. Fong, and S. G. Young Eliminating the Synthesis of Mature Lamin A Reduces Disease Phenotypes in Mice Carrying a Hutchinson-Gilford Progeria Syndrome Allele J. Biol. Chem., March 14, 2008; 283(11): 7094 - 7099. [Abstract] [Full Text] [PDF]

				K. Gehrig, R. B. Cornell, and N. D. Ridgway Expansion of the Nucleoplasmic Reticulum Requires the Coordinated Activity of Lamins and CTP:Phosphocholine Cytidylyltransferase {alpha} Mol. Biol. Cell, January 1, 2008; 19(1): 237 - 247. [Abstract] [Full Text] [PDF]

				M. W. Kieran, L. Gordon, and M. Kleinman New Approaches to Progeria Pediatrics, October 1, 2007; 120(4): 834 - 841. [Abstract] [Full Text] [PDF]

				J. Afilalo, I. A. Sebag, L. E. Chalifour, D. Rivas, R. Akter, K. Sharma, and G. Duque Age-related changes in lamin A/C expression in cardiomyocytes Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1451 - H1456. [Abstract] [Full Text] [PDF]

				Q. Liu, N. Pante, T. Misteli, M. Elsagga, M. Crisp, D. Hodzic, B. Burke, and K. J. Roux Functional association of Sun1 with nuclear pore complexes J. Cell Biol., August 27, 2007; 178(5): 785 - 798. [Abstract] [Full Text] [PDF]

				B. C. Capell, F. S. Collins, and E. G. Nabel Mechanisms of Cardiovascular Disease in Accelerated Aging Syndromes Circ. Res., July 6, 2007; 101(1): 13 - 26. [Abstract] [Full Text] [PDF]

				J. Y. Ji, R. T. Lee, L. Vergnes, L. G. Fong, C. L. Stewart, K. Reue, S. G. Young, Q. Zhang, C. M. Shanahan, and J. Lammerding Cell Nuclei Spin in the Absence of Lamin B1 J. Biol. Chem., July 6, 2007; 282(27): 20015 - 20026. [Abstract] [Full Text] [PDF]

				S. G. Young, M. Meta, S. H. Yang, and L. G. Fong Prelamin A Farnesylation and Progeroid Syndromes J. Biol. Chem., December 29, 2006; 281(52): 39741 - 39745. [Abstract] [Full Text] [PDF]