Nuclear Envelope Assembly and Disassembly During the Cell Cycle

Abstract

The nuclear envelope of metazoa breaks down at the onset of mitosis and reassembles at the end of mitosis. This process is mainly controlled by the cyclin‐dependent kinase that phosphorylates inner nuclear membrane (INM) proteins to disrupt their association with chromatin and to disintegrate the nuclear lamina. Upon nuclear envelope breakdown, the nuclear membrane and integral nuclear membrane proteins retract into the endoplasmic reticulum (ER), whereas other peripheral nuclear membrane proteins and some components of the nuclear pore complex become disperse in the cytosol. At late anaphase, inactivation of the cyclin‐dependent kinase and dephosphorylation of INM proteins allow these proteins to bind the chromatin and brings the ER membrane to the chromatin surface to initiate nuclear envelope assembly around the compact chromosome mass. The nuclear envelope disassembly and assembly are thus coordinated with the segregation of sister chromatids in each cell division cycle to maintain genome stability.

Key Concepts:

  • The nuclear envelope is a dynamic structure that is continuous with the ER.

  • The INM proteins associate with and organise the chromatin.

  • The disassembly of nuclear envelope is triggered by the cyclin‐dependent kinase at the onset of mitosis.

  • Phosphorylation of INM proteins disrupts their interaction with chromatin.

  • Nuclear envelope breakdown is essential for sister chromatid segregation.

  • Integral nuclear membrane proteins diffuse into the ER after nuclear envelope breakdown.

  • The nuclear envelope reassembles around compact chromosome mass at late anaphase/telophase.

  • Nuclear envelope reassembly is mediated by multiple interactions of the INM proteins with chromatin.

  • Dephosphorylation of INM proteins at late anaphase/telophase is required for nuclear envelope reassembly.

Keywords: nuclear envelope; endoplasmic reticulum; mitosis; inner nuclear membrane protein; phosphorylation

Figure 1.

General structure of the NE and its major components. The NE is composed of a double membrane that is joined at the nuclear pore complex (NPC) insertion site and bridged by the SUN–KASH complex. The ONM is continuous with the ER dubbed with ribosomes, and the INM is enriched for integral membrane proteins such as LBR, LAP1/2, emerin, and MAN1. The latter three contain LEM domain that binds BAF. Underlying the INM is the nuclear lamina made of lamin proteins. The nuclear lamina and INM proteins mediate chromatin association with the NE.

Figure 2.

Process of NE disassembly. NEBD begins with tearing and stretching of the NE by microtubules and the motor protein dynein. Upon phosphorylation by mitotic kinases, the nuclear lamina disassembles and the INM proteins detach from the chromatin. The nuclear membrane and its integral membrane proteins then disperse throughout the ER, whereas the peripheral nuclear membrane proteins become cytosolic.

Figure 3.

Two distinct mechanisms of NE assembly. LBR and lamin B first target the ER to the rim of the anaphase chromosome mass, followed by membrane expansion toward the polar and equatorial regions. After the initial binding to the chromatin, LBR and lamin B become quickly enriched on the chromosomal side of the reforming NE. On the other hand, microtubules localise BAF to the core region of the chromosome mass near the spindle microtubules. BAF recruits LEM domain proteins to the core to form a stable higher‐order structure that eliminates microtubules from the chromosome. All these proteins become evenly distributed on the complete NE.

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References

Anderson DJ and Hetzer MW (2007) Nuclear envelope formation by chromatin‐mediated reorganization of the endoplasmic reticulum. Nature Cell Biology 9: 1160–1166.

Anderson DJ and Hetzer MW (2008) Reshaping of the endoplasmic reticulum limits the rate for nuclear envelope formation. Journal of Cell Biology 182: 911–924.

Anderson DJ, Vargas JD, Hsiao JP and Hetzer MW (2009) Recruitment of functionally distinct membrane proteins to chromatin mediates nuclear envelope formation in vivo. Journal of Cell Biology 186: 183–191.

Beaudouin J, Gerlich D, Daigle N, Eils R and Ellenberg J (2002) Nuclear envelope breakdown proceeds by microtubule‐induced tearing of the lamina. Cell 108: 83–96.

Bione S, Maestrini E, Rivella S et al. (1994) Identification of a novel X‐linked gene responsible for Emery–Dreifuss muscular dystrophy. Nature Genetics 8: 323–327.

Buch C, Lindberg R, Figueroa R et al. (2009) An integral protein of the inner nuclear membrane localizes to the mitotic spindle in mammalian cells. Journal of Cell Science 122: 2100–2107.

Carmena M, Ruchaud S and Earnshaw WC (2009) Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Current Opinion in Cell Biology 21: 796–805.

Dechat T, Gotzmann J, Stockinger A et al. (1998) Detergent‐salt resistance of LAP2alpha in interphase nuclei and phosphorylation‐dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dynamics. EMBO Journal 17: 4887–4902.

Dreger M, Bengtsson L, Schoneberg T, Otto H and Hucho F (2001) Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane. Proceedings of the National Academy of Sciences of the USA 98: 11943–11948.

Dultz E, Zanin E, Wurzenberger C et al. (2008) Systematic kinetic analysis of mitotic dis‐ and reassembly of the nuclear pore in living cells. Journal of Cell Biology 180: 857–865.

Ellenberg J, Siggia ED, Moreira JE et al. (1997) Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis. Journal of Cell Biology 138: 1193–1206.

Foisner R and Gerace L (1993) Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell 73: 1267–1279.

Furukawa K, Pante N, Aebi U and Gerace L (1995) Cloning of a cDNA for lamina‐associated polypeptide 2 (LAP2) and identification of regions that specify targeting to the nuclear envelope. EMBO Journal 14: 1626–1636.

Georgatos SD, Pyrpasopoulou A and Theodoropoulos PA (1997) Nuclear envelope breakdown in mammalian cells involves stepwise lamina disassembly and microtubule‐drive deformation of the nuclear membrane. Journal of Cell Science 110: 2129–2140.

Gong D, Pomerening JR, Myers JW et al. (2007) Cyclin A2 regulates nuclear‐envelope breakdown and the nuclear accumulation of cyclin B1. Current Biology 17: 85–91.

Goss VL, Hocevar BA, Thompson LJ et al. (1994) Identification of nuclear beta II protein kinase C as a mitotic lamin kinase. Journal of Biological Chemistry 269: 19074–19080.

Gudise S, Figueroa RA, Lindberg R, Larsson V and Hallberg E (2011) Samp1 is functionally associated with the LINC complex and A‐type lamina networks. Journal of Cell Science 124: 2077–2085.

Haraguchi T, Kojidani T, Koujin T et al. (2008) Live cell imaging and electron microscopy reveal dynamic processes of BAF‐directed nuclear envelope assembly. Journal of Cell Science 121: 2540–2554.

Haraguchi T, Koujin T, Hayakawa T et al. (2000) Live fluorescence imaging reveals early recruitment of emerin, LBR, RanBP2, and Nup153 to reforming functional nuclear envelopes. Journal of Cell Science 113: 779–794.

Haraguchi T, Koujin T, Segura‐Totten M et al. (2001) BAF is required for emerin assembly into the reforming nuclear envelope. Journal of Cell Science 114: 4575–4585.

Heald R and McKeon F (1990) Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis. Cell 61: 579–589.

Hetzer MW, Walther TC and Mattaj IW (2005) Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annual Review of Cell and Developmental Biology 21: 347–380.

Laurell E, Beck K, Krupina K et al. (2011) Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry. Cell 144: 539–550.

Lee KK, Haraguchi T, Lee RS et al. (2001) Distinct functional domains in emerin bind lamin A and DNA‐bridging protein BAF. Journal of Cell Science 114: 4567–4573.

Lin F, Blake DL, Callebaut I et al. (2000) MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina‐associated polypeptide 2 and emerin. Journal of Biological Chemistry 275: 4840–4847.

Lu L, Ladinsky MS and Kirchhausen T (2009) Cisternal organization of the endoplasmic reticulum during mitosis. Molecular Biology of the Cell 20: 3471–3480.

Lu L, Ladinsky MS and Kirchhausen T (2011) Formation of the postmitotic nuclear envelope from extended ER cisternae precedes nuclear pore assembly. Journal of Cell Biology 194: 425–440.

McCullough S and Lucocq J (2005) Endoplasmic reticulum positioning and partitioning in mitotic HeLa cells. Journal of Anatomy 206: 415–425.

Mora‐Bermudez F, Gerlich D and Ellenberg J (2007) Maximal chromosome compaction occurs by axial shortening in anaphase and depends on Aurora kinase. Nature Cell Biology 9: 822–831.

Muhlhausser P and Kutay U (2007) An in vitro nuclear disassembly system reveals a role for the RanGTPase system and microtubule‐dependent steps in nuclear envelope breakdown. Journal of Cell Biology 178: 595–610.

Newport J (1987) Nuclear reconstitution in vitro: stages of assembly around protein‐free DNA. Cell 48: 205–217.

Newport J and Spann T (1987) Disassembly of the nucleus in mitotic extracts: membrane vesicularization, lamin disassembly, and chromosome condensation are independent processes. Cell 48: 219–230.

Ohsugi M, Adachi K, Horai R et al. (2008) Kid‐mediated chromosome compaction ensures proper nuclear envelope formation. Cell 132: 771–782.

Onischenko EA, Crafoord E and Hallberg E (2007) Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex. Experimental Cell Research 313: 2744–2751.

Onischenko EA, Gubanova NV, Kiseleva EV and Hallberg E (2005) Cdk1 and okadaic acid‐sensitive phosphatases control assembly of nuclear pore complexes in Drosophila embryos. Molecular Biology of the Cell 16: 5152–5162.

Portier N, Audhya A, Maddox PS et al. (2007) A microtubule‐independent role for centrosomes and aurora a in nuclear envelope breakdown. Developmental Cell 12: 515–529.

Puhka M, Vihinen H, Joensuu M and Jokitalo E (2007) Endoplasmic reticulum remains continuous and undergoes sheet‐to‐tubule transformation during cell division in mammalian cells. Journal of Cell Biology 179: 895–909.

Salina D, Bodoor K, Eckley DM et al. (2002) Cytoplasmic dynein as a facilitator of nuclear envelope breakdown. Cell 108: 97–107.

Schirmer EC, Florens L, Guan T, Yates JR and Gerace L (2003) Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 301: 1380–1382.

Shibata Y, Voss C, Rist JM et al. (2008) The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum. Journal of Biological Chemistry 283: 18892–18904.

Shimi T, Koujin T, Segura‐Totten M et al. (2004) Dynamic interaction between BAF and emerin revealed by FRAP, FLIP, and FRET analyses in living HeLa cells. Journal of Structural Biology 147: 31–41.

Starr DA and Fridolfsson HN (2010) Interactions between nuclei and the cytoskeleton are mediated by SUN‐KASH nuclear‐envelope bridges. Annual Review of Cell and Developmental Biology 26: 421–444.

Takano M, Koyama Y, Ito H et al. (2004) Regulation of binding of lamin B receptor to chromatin by SR protein kinase and cdc2 kinase in Xenopus egg extracts. Journal of Biological Chemistry 279: 13265–13271.

Thompson LJ and Fields AP (1996) betaII protein kinase C is required for the G2/M phase transition of cell cycle. Journal of Biological Chemistry 271: 15045–15053.

Tseng LC and Chen RH (2011) Temporal control of nuclear envelope assembly by phosphorylation of lamin B receptor. Molecular Biology of the Cell 22: 3306–3317.

Voeltz GK, Prinz WA, Shibata Y, Rist JM and Rapoport TA (2006) A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 124: 573–586.

Wilson KL and Newport J (1988) A trypsin‐sensitive receptor on membrane vesicles is required for nuclear envelope formation in vitro. Journal of Cell Biology 107: 57–68.

Worman HJ, Yuan J, Blobel G and Georgatos SD (1988) A lamin B receptor in the nuclear envelope. Proceedings of the National Academy of Sciences of the USA 85: 8531–8534.

Wu JQ, Guo JY, Tang W et al. (2009) PP1‐mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor‐1 and PP1 phosphorylation. Nature Cell Biology 11: 644–651.

Yang L, Guan T and Gerace L (1997) Integral membrane proteins of the nuclear envelope are dispersed throughout the endoplasmic reticulum during mitosis. Journal of Cell Biology 137: 1199–1210.

Ye Q, Barton RM and Worman HJ (1998) Nuclear lamin‐binding proteins. Subcellular Biochemistry 31: 587–610.

Further Reading

Burke B and Stewart CL (2002) Life at the edge: the nuclear envelope and human disease. Nature Reviews Molecular Cell Biology 3: 575–585.

Dechat T, Vlcek S and Foisner R (2000) Review: lamina‐associated polypeptide 2 isoforms and related proteins in cell cycle‐dependent nuclear structure dynamics. Journal of Structrual Biology 129: 335–345.

Dittmer TA and Misteli T (2011) The lamin protein family. Genome Biology 12: 222.

Doucet CM and Hetzer MW (2010) Nuclear pore biogenesis into an intact nuclear envelope. Chromosoma 119: 469–477.

Holmer L and Worman HJ (2001) Inner nuclear membrane proteins: functions and targeting. Cellular and Molecular Life Sciences 58: 1741–1747.

Shibata Y, Voeltz GK and Rapoport TA (2006) Rough sheets and smooth tubules. Cell 126: 435–439.

Smythe C and Newport JW (1991) Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts. Methods in Cell Biology 35: 449–468.

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Chen, Rey‐Huei(Sep 2012) Nuclear Envelope Assembly and Disassembly During the Cell Cycle. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022532]