This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Haque, F.
Right arrow Articles by Shackleton, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haque, F.
Right arrow Articles by Shackleton, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3738-3751, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3738-3751.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

SUN1 Interacts with Nuclear Lamin A and Cytoplasmic Nesprins To Provide a Physical Connection between the Nuclear Lamina and the Cytoskeleton

Farhana Haque,1 David J. Lloyd,1,{dagger} Dawn T. Smallwood,1 Carolyn L. Dent,1 Catherine M. Shanahan,3 Andrew M. Fry,2 Richard C. Trembath,1 and Sue Shackleton1,2*

Department of Genetics,1 Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,2 Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom3

Received 30 June 2005/ Returned for modification 12 August 2005/ Accepted 24 February 2006

Nuclear migration and positioning within cells are critical for many developmental processes and are governed by the cytoskeletal network. Although mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links a novel family of nuclear envelope (NE) proteins that share a conserved C-terminal SUN (Sad1/UNC-84 homology) domain. Analysis of Caenorhabditis elegans mutants has implicated UNC-84 in actin-mediated nuclear positioning by regulating NE anchoring of a giant actin-binding protein, ANC-1. Here, we report the identification of SUN1 as a lamin A-binding protein in a yeast two-hybrid screen. We demonstrate that SUN1 is an integral membrane protein located at the inner nuclear membrane. While the N-terminal domain of SUN1 is responsible for detergent-resistant association with the nuclear lamina and lamin A binding, lamin A/C expression is not required for SUN1 NE localization. Furthermore, SUN1 does not interact with type B lamins, suggesting that NE localization is ensured by binding to an additional nuclear component(s), most likely chromatin. Importantly, we find that the luminal C-terminal domain of SUN1 interacts with the mammalian ANC-1 homologs nesprins 1 and 2 via their conserved KASH domain. Our data provide evidence of a physical nuclear-cytoskeletal connection that is likely to be a key mechanism in nuclear-cytoplasmic communication and regulation of nuclear position.

* Corresponding author. Mailing address: Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom. Phone: 44 116 229 7029. Fax: 44 116 229 7058. E-mail: ss115{at}le.ac.uk.

{dagger} Present address: Genomics Institute of the Novartis Research Foundation, San Diego, CA 92122.

Molecular and Cellular Biology, May 2006, p. 3738-3751, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3738-3751.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ostlund, C., Folker, E. S., Choi, J. C., Gomes, E. R., Gundersen, G. G., Worman, H. J. (2009). Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton (LINC) complex proteins. J. Cell Sci. 122: 4099-4108 [Abstract] [Full Text]  
  • Minn, I., Rolls, M. M., Hanna-Rose, W., Malone, C. J. (2009). SUN-1 and ZYG-12, Mediators of Centrosome-Nucleus Attachment, Are a Functional SUN/KASH Pair in Caenorhabditis elegans. Mol. Biol. Cell 20: 4586-4595 [Abstract] [Full Text]  
  • Razafsky, D., Hodzic, D. (2009). Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections. JCB 186: 461-472 [Abstract] [Full Text]  
  • Lei, K., Zhang, X., Ding, X., Guo, X., Chen, M., Zhu, B., Xu, T., Zhuang, Y., Xu, R., Han, M. (2009). SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proc. Natl. Acad. Sci. USA 106: 10207-10212 [Abstract] [Full Text]  
  • Mejat, A., Decostre, V., Li, J., Renou, L., Kesari, A., Hantai, D., Stewart, C. L., Xiao, X., Hoffman, E., Bonne, G., Misteli, T. (2009). Lamin A/C-mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy. JCB 184: 31-44 [Abstract] [Full Text]  
  • Oza, P., Jaspersen, S. L., Miele, A., Dekker, J., Peterson, C. L. (2009). Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 23: 912-927 [Abstract] [Full Text]  
  • Chi, Y.-H., Cheng, L. I., Myers, T., Ward, J. M., Williams, E., Su, Q., Faucette, L., Wang, J.-Y., Jeang, K.-T. (2009). Requirement for Sun1 in the expression of meiotic reproductive genes and piRNA. Development 136: 965-973 [Abstract] [Full Text]  
  • Starr, D. A. (2009). A nuclear-envelope bridge positions nuclei and moves chromosomes. J. Cell Sci. 122: 577-586 [Abstract] [Full Text]  
  • Roux, K. J., Crisp, M. L., Liu, Q., Kim, D., Kozlov, S., Stewart, C. L., Burke, B. (2009). Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization. Proc. Natl. Acad. Sci. USA 106: 2194-2199 [Abstract] [Full Text]  
  • Puckelwartz, M. J., Kessler, E., Zhang, Y., Hodzic, D., Randles, K. N., Morris, G., Earley, J. U., Hadhazy, M., Holaska, J. M., Mewborn, S. K., Pytel, P., McNally, E. M. (2009). Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice. Hum Mol Genet 18: 607-620 [Abstract] [Full Text]  
  • Holaska, J. M. (2008). Emerin and the Nuclear Lamina in Muscle and Cardiac Disease. Circ. Res. 103: 16-23 [Abstract] [Full Text]  
  • Dahl, K. N., Ribeiro, A. J.S., Lammerding, J. (2008). Nuclear Shape, Mechanics, and Mechanotransduction. Circ. Res. 102: 1307-1318 [Abstract] [Full Text]  
  • Dechat, T., Pfleghaar, K., Sengupta, K., Shimi, T., Shumaker, D. K., Solimando, L., Goldman, R. D. (2008). Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. 22: 832-853 [Abstract] [Full Text]  
  • Bengtsson, L., Otto, H. (2008). LUMA interacts with emerin and influences its distribution at the inner nuclear membrane. J. Cell Sci. 121: 536-548 [Abstract] [Full Text]  
  • Bupp, J. M., Martin, A. E., Stensrud, E. S., Jaspersen, S. L. (2007). Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3. JCB 179: 845-854 [Abstract] [Full Text]  
  • Zhang, Q., Bethmann, C., Worth, N. F., Davies, J. D., Wasner, C., Feuer, A., Ragnauth, C. D., Yi, Q., Mellad, J. A., Warren, D. T., Wheeler, M. A., Ellis, J. A., Skepper, J. N., Vorgerd, M., Schlotter-Weigel, B., Weissberg, P. L., Roberts, R. G., Wehnert, M., Shanahan, C. M. (2007). Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet 16: 2816-2833 [Abstract] [Full Text]  
  • Stewart, C. L., Roux, K. J., Burke, B. (2007). Blurring the Boundary: The Nuclear Envelope Extends Its Reach. Science 318: 1408-1412 [Abstract] [Full Text]  
  • Ketema, M., Wilhelmsen, K., Kuikman, I., Janssen, H., Hodzic, D., Sonnenberg, A. (2007). Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin. J. Cell Sci. 120: 3384-3394 [Abstract] [Full Text]  
  • Chi, Y.-H., Haller, K., Peloponese, J.-M. Jr., Jeang, K.-T. (2007). Histone Acetyltransferase hALP and Nuclear Membrane Protein hsSUN1 Function in De-condensation of Mitotic Chromosomes. J. Biol. Chem. 282: 27447-27458 [Abstract] [Full Text]  
  • Liu, Q., Pante, N., Misteli, T., Elsagga, M., Crisp, M., Hodzic, D., Burke, B., Roux, K. J. (2007). Functional association of Sun1 with nuclear pore complexes. JCB 178: 785-798 [Abstract] [Full Text]  
  • Ji, J. Y., Lee, R. T., Vergnes, L., Fong, L. G., Stewart, C. L., Reue, K., Young, S. G., Zhang, Q., Shanahan, C. M., Lammerding, J. (2007). Cell Nuclei Spin in the Absence of Lamin B1. J. Biol. Chem. 282: 20015-20026 [Abstract] [Full Text]  
  • Morris, J. B., Hofemeister, H., O'Hare, P. (2007). Herpes Simplex Virus Infection Induces Phosphorylation and Delocalization of Emerin, a Key Inner Nuclear Membrane Protein. J. Virol. 81: 4429-4437 [Abstract] [Full Text]  
  • Schmitt, J., Benavente, R., Hodzic, D., Hoog, C., Stewart, C. L., Alsheimer, M. (2007). Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proc. Natl. Acad. Sci. USA 104: 7426-7431 [Abstract] [Full Text]  
  • Wilhelmsen, K., Ketema, M., Truong, H., Sonnenberg, A. (2006). KASH-domain proteins in nuclear migration, anchorage and other processes. J. Cell Sci. 119: 5021-5029 [Abstract] [Full Text]  
  • Jaspersen, S. L., Martin, A. E., Glazko, G., Giddings, T. H. Jr., Morgan, G., Mushegian, A., Winey, M. (2006). The Sad1-UNC-84 homology domain in Mps3 interacts with Mps2 to connect the spindle pole body with the nuclear envelope. JCB 174: 665-675 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»