J. Cell Biol., Volume 144, Number 6, March 22, 1999 1083-1096

Roles of LAP2 Proteins in Nuclear Assembly and DNA Replication: Truncated LAP2 Proteins Alter Lamina Assembly, Envelope Formation, Nuclear Size, and DNA Replication Efficiency in Xenopus laevis Extracts

Tracey Michele Gant,^* Crafford A. Harris, and Katherine L. Wilson^*

^* Department of Cell Biology and Anatomy,  The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and  R.W.  Johnson Pharmaceutical Research Institute Drug Discovery, Raritan, New Jersey 08869

Humans express three major splicing isoforms of LAP2, a lamin- and chromatin-binding nuclear protein. LAP2 and  are integral membrane proteins, whereas  is intranuclear. When truncated recombinant human LAP2 proteins were added to cell-free Xenopus laevis nuclear assembly reactions at high concentrations, a domain common to all LAP2 isoforms (residues 1-187) inhibited membrane binding to chromatin, whereas the chromatin- and lamin-binding region (residues 1-408) inhibited chromatin expansion. At lower concentrations of the common domain, membranes attached to chromatin with a unique scalloped morphology, but these nuclei neither accumulated lamins nor replicated. At lower concentrations of the chromatin- and lamin-binding region, nuclear envelopes and lamins assembled, but nuclei failed to enlarge and replicated on average 2.5-fold better than controls. This enhancement was not due to rereplication, as shown by density substitution experiments, suggesting the hypothesis that LAP2 is a downstream effector of lamina assembly in promoting replication competence. Overall, our findings suggest that LAP2 proteins mediate membrane-chromatin attachment and lamina assembly, and may promote replication by influencing chromatin structure.

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

This article has been cited by other articles:

• Salpingidou, G., Rzepecki, R., Kiseleva, E., Lyon, C., Lane, B., Fusiek, K., Golebiewska, A., Drummond, S., Allen, T., Ellis, J. A., Smythe, C., Goldberg, M. W., Hutchison, C. J. (2008). NEP-A and NEP-B both contribute to nuclear pore formation in Xenopus eggs and oocytes. J. Cell Sci. 121: 706-716 [Abstract] [Full Text]  
• Vaillant, D. C., Paulin-Levasseur, M. (2008). Evaluation of Mammalian Cell-free Systems of Nuclear Disassembly and Assembly. J. Histochem. Cytochem. 56: 157-173 [Abstract] [Full Text]  
• Haraguchi, T., Koujin, T., Osakada, H., Kojidani, T., Mori, C., Masuda, H., Hiraoka, Y. (2007). Nuclear localization of barrier-to-autointegration factor is correlated with progression of S phase in human cells. J. Cell Sci. 120: 1967-1977 [Abstract] [Full Text]  
• Broers, J. L. V., Ramaekers, F. C. S., Bonne, G., Yaou, R. B., Hutchison, C. J. (2006). Nuclear lamins: laminopathies and their role in premature ageing.. Physiol. Rev. 86: 967-1008 [Abstract] [Full Text]  
• O'Brien, L. L., Wiese, C. (2006). TPX2 is required for postmitotic nuclear assembly in cell-free Xenopus laevis egg extracts. J. Cell Biol. 173: 685-694 [Abstract] [Full Text]  
• Dechat, T., Gajewski, A., Korbei, B., Gerlich, D., Daigle, N., Haraguchi, T., Furukawa, K., Ellenberg, J., Foisner, R. (2004). LAP2{alpha} and BAF transiently localize to telomeres and specific regions on chromatin during nuclear assembly. J. Cell Sci. 117: 6117-6128 [Abstract] [Full Text]  
• Ralle, T., Grund, C., Franke, W. W., Stick, R. (2004). Intranuclear membrane structure formations by CaaX-containing nuclear proteins. J. Cell Sci. 117: 6095-6104 [Abstract] [Full Text]  
• Harel, A., Chan, R. C., Lachish-Zalait, A., Zimmerman, E., Elbaum, M., Forbes, D. J. (2003). Importin {beta} Negatively Regulates Nuclear Membrane Fusion and Nuclear Pore Complex Assembly. Mol. Biol. Cell 14: 4387-4396 [Abstract] [Full Text]  
• Furukawa, K., Sugiyama, S., Osouda, S., Goto, H., Inagaki, M., Horigome, T., Omata, S., McConnell, M., Fisher, P. A., Nishida, Y. (2003). Barrier-to-autointegration factor plays crucial roles in cell cycle progression and nuclear organization in Drosophila. J. Cell Sci. 116: 3811-3823 [Abstract] [Full Text]  
• Fischer, A. H., Taysavang, P., Jhiang, S. M. (2003). Nuclear Envelope Irregularity Is Induced by RET/PTC During Interphase. Am. J. Pathol. 163: 1091-1100 [Abstract] [Full Text]  
• Schoft, V. K., Beauvais, A. J., Lang, C., Gajewski, A., Prufert, K., Winkler, C., Akimenko, M.-A., Paulin-Levasseur, M., Krohne, G. (2003). The lamina-associated polypeptide 2 (LAP2) isoforms {beta}, {gamma} and {omega} of zebrafish: developmental expression and behavior during the cell cycle. J. Cell Sci. 116: 2505-2517 [Abstract] [Full Text]  
• Kato, N., Lam, E. (2003). Chromatin of endoreduplicated pavement cells has greater range of movement than that of diploid guard cells in Arabidopsis thaliana. J. Cell Sci. 116: 2195-2201 [Abstract] [Full Text]  
• Steen, R. L., Beullens, M., Landsverk, H. B., Bollen, M., Collas, P. (2003). AKAP149 is a novel PP1 specifier required to maintain nuclear envelope integrity in G1 phase. J. Cell Sci. 116: 2237-2246 [Abstract] [Full Text]  
• Martins, S., Eikvar, S., Furukawa, K., Collas, P. (2003). HA95 and LAP2{beta} mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication. J. Cell Biol. 160: 177-188 [Abstract] [Full Text]  
• Markiewicz, E., Dechat, T., Foisner, R., Quinlan, Roy. A, Hutchison, C. J. (2002). Lamin A/C Binding Protein LAP2alpha Is Required for Nuclear Anchorage of Retinoblastoma Protein. Mol. Biol. Cell 13: 4401-4413 [Abstract] [Full Text]  
• Segura-Totten, M., Kowalski, A. K., Craigie, R., Wilson, K. L. (2002). Barrier-to-autointegration factor: major roles in chromatin decondensation and nuclear assembly. J. Cell Biol. 158: 475-485 [Abstract] [Full Text]  
• Drummond, S. P., Wilson, K. L. (2002). Interference with the cytoplasmic tail of gp210 disrupts "close apposition" of nuclear membranes and blocks nuclear pore dilation. J. Cell Biol. 158: 53-62 [Abstract] [Full Text]  
• Vlcek, S., Korbei, B., Foisner, R. (2002). Distinct Functions of the Unique C Terminus of LAP2alpha in Cell Proliferation and Nuclear Assembly. J. Biol. Chem. 277: 18898-18907 [Abstract] [Full Text]  
• Nili, E., Cojocaru, G. S., Kalma, Y., Ginsberg, D., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Berger, R., Shaklai, S., Amariglio, N., Brok-Simoni, F., Simon, A. J., Rechavi, G. (2002). Nuclear membrane protein LAP2{beta} mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less). J. Cell Sci. 114: 3297-3307 [Abstract] [Full Text]  
• Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K., Spann, T. P. (2002). Nuclear lamins: building blocks of nuclear architecture. Genes Dev. 16: 533-547 [Full Text]  
• Lopez-Soler, R. I., Moir, R. D., Spann, T. P., Stick, R., Goldman, R. D. (2001). A role for nuclear lamins in nuclear envelope assembly. J. Cell Biol. 154: 61-70 [Abstract] [Full Text]  
• Hutchison, C., Alvarez-Reyes, M, Vaughan, O. (2001). Lamins in disease: why do ubiquitously expressed nuclear envelope proteins give rise to tissue-specific disease phenotypes?. J. Cell Sci. 114: 9-19 [Abstract]  
• Moir, R. D., Yoon, M., Khuon, S., Goldman, R. D. (2000). Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells. J. Cell Biol. 151: 1155-1168 [Abstract] [Full Text]  
• Zheng, R., Ghirlando, R., Lee, M. S., Mizuuchi, K., Krause, M., Craigie, R. (2000). Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex. Proc. Natl. Acad. Sci. USA 10.1073/pnas.150240197v1 [Abstract] [Full Text]  
• Swanson, C., Ross, J., Jackson, P. K. (2000). Nuclear accumulation of cyclin E/Cdk2 triggers a concentration-dependent switch for the destruction of p27Xic1. Proc. Natl. Acad. Sci. USA 97: 7796-7801 [Abstract] [Full Text]  
• Martins, S., Eide, T, Steen, R., Jahnsen, T, Skalhegg B, S, Collas, P (2000). HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics. J. Cell Sci. 113: 3703-3713 [Abstract]  
• Gotzmann, J, Vlcek, S, Foisner, R (2000). Caspase-mediated cleavage of the chromosome-binding domain of lamina-associated polypeptide 2 alpha. J. Cell Sci. 113: 3769-3780 [Abstract]  
• Dechat, T, Korbei, B, Vaughan, O., Vlcek, S, Hutchison, C., Foisner, R (2000). Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. J. Cell Sci. 113: 3473-3484 [Abstract]  
• Haraguchi, T, Koujin, T, Hayakawa, T, Kaneda, T, Tsutsumi, C, Imamoto, N, Akazawa, C, Sukegawa, J, Yoneda, Y, Hiraoka, Y (2000). Live fluorescence imaging reveals early recruitment of emerin, LBR, RanBP2, and Nup153 to reforming functional nuclear envelopes. J. Cell Sci. 113: 779-794 [Abstract]  
• Rolls, M. M., Stein, P. A., Taylor, S. S., Ha, E., McKeon, F., Rapoport, T. A. (1999). A Visual Screen of a GFP-fusion Library Identifies a New Type of Nuclear Envelope Membrane Protein. J. Cell Biol. 146: 29-44 [Abstract] [Full Text]  
• Zheng, R., Ghirlando, R., Lee, M. S., Mizuuchi, K., Krause, M., Craigie, R. (2000). Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex. Proc. Natl. Acad. Sci. USA 97: 8997-9002 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents