Lamina-associated polypeptide 2 (LAP2) is an integral membrane protein of the inner nuclear membrane that binds to both lamin B and chromatin and has a putative role in nuclear envelope (NE) organization. We found that microinjection of a recombinant polypeptide comprising the nucleoplasmic domain of rat LAP2 (residues 1–398) into metaphase HeLa cells does not affect the reassembly of transport-competent nuclei containing NEs and lamina, but strongly inhibits nuclear volume increase. This effect appears to be specifically due to lamin binding, because it also is caused by microinjection of the minimal lamin-binding region of LAP2 (residues 298–373) but not by the chromatin-binding domain (residues 1–88). Injection of the lamin-binding region of rat LAP2 into early G1 phase HeLa cells also strongly affects nuclear growth; it almost completely prevents the threefold nuclear volume increase that normally occurs during the ensuing 10 h. Moreover, injection of the fragment during early G1 phase strongly inhibits entry of cells into S phase, whereas injection during S phase has no apparent effect on ongoing DNA replication. Since the lamin-binding fragment of LAP2 most likely acts by inhibiting dynamics of the nuclear lamina, our results suggest that a normal function of LAP2 involves regulation of nuclear lamina growth. These data also suggest that lamina dynamics are required for growth of the NE and for nuclear volume increase during the cell cycle, and that progression into S phase is dependent on the acquisition of a certain nuclear volume.
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1 December 1997
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December 01 1997
Lamin-binding Fragment of LAP2 Inhibits Increase in Nuclear Volume during the Cell Cycle and Progression into S Phase
Li Yang,
Li Yang
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
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Tinglu Guan,
Tinglu Guan
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
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Larry Gerace
Larry Gerace
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
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Li Yang
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
Tinglu Guan
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
Larry Gerace
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
Address all correspondence to L. Gerace, Departments of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Tel.: (619) 784-8514. Fax: (619) 784-9132.
Received:
August 14 1997
Revision Received:
September 24 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 139 (5): 1077–1087.
Article history
Received:
August 14 1997
Revision Received:
September 24 1997
Citation
Li Yang, Tinglu Guan, Larry Gerace; Lamin-binding Fragment of LAP2 Inhibits Increase in Nuclear Volume during the Cell Cycle and Progression into S Phase . J Cell Biol 1 December 1997; 139 (5): 1077–1087. doi: https://doi.org/10.1083/jcb.139.5.1077
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