Nuclek

envelope George

Northwestern

University

structure

N. Dessev

Medical

School,

Chicago,

Illinois, USA

The past 18 months have seen significant advances in our knowledge of the constituents of the nuclear envelope, their interactions during interphase and the mechanisms involved in their mitotic dynamics. Although most of the new data are in general agreement with, and contribute detail to, our traditional image of the nuclear envelope, a few observations appear to mark the beginning of new and important directions in research. Current

Opinion

in Cell Biology

Introduction

in their a-helical domains. Not all lamins in a single nucleus are necessarily organized as dimers; the NL of clam oocytes contains lamin monomers [I]. The presence of unpaired lamins with ‘unsaturated’ a-helical domains may reflect irregularities formed during the nuclear growth, or may have some unknown structural role such as interaction with non-lamin components of the NE.

The nuclear envelope (NE) is a complex organelle consisting of a protein meshwork termed the nuclear lamina (NL), a double lipid-based nuclear membrane and nuclear pore complexes (NPC). The NE physically separates the cell into nuclear and cytoplasmic compartments and plays a major role in the communication between them. In most eukaryotic cells, the NE is disassembled at the beginning of mitosis, concomitantly with an increase in lamin phosphorylation, and is reformed around the decondensing chromosomes as cells enter interphase. It has been suggested that the NL serves as a framework imparting stability to the NE and that it plays a role in the structural organization of chromatin in the interphase nucleus; it is thus involved in the regulation of basic cellular activities such as chromosome replication and gene expression. The results obtained during the past 18 months have made significant contributions to the understanding of a number of structural and functional aspects of the NE. This reviewwill focus on selected recent publications that characterize the present state of NE-related research.

Nuclear lamina dynamics

structure

At the second level of organization, lamin dimers as sociate longitudinally, head-to-tail, forming filamentous structures (type II interactions) [2*-l. At the third level, these filaments further associate laterally (type III interactions) to form thicker Iilamentous structures (in rdtloo)and paractystal formations (it1 zlitro) in which the lamin dimers are arranged in a half-staggered manner. In some cases these structures appear very similar to the typical lo-run intermediate filaments [ 2**]. This arrangement gives rise to the characteristic 25.nm axial repeat pattern, visible by electron microscopy as stain-exclusion zones [ 2**]. Information about the interacting sites in the lamin molecules involved in these three levels of organization has come from studies on NL disassembly [5,6]. Using expression of mutant human lamins in Chinese hamster ovary cells, Heald and McKeon [5] found that changing serines 22 and 392 into alanines, (which cannot be phosphorylated), blocks the disassembly of the NL during mitosis. These results are supported by direct sequencing data from Ward and Kirschner [6]. The fact that the phosphotylation of only two out of more than 60 serines in the lamin molecule is sufficient to cause a dramatic structural effect such as NL disassembly suggests how powerful this modification can be in regulating protein-protein interactions. The two important serines have been localized in the amino- and carboxylterminal non-helical parts of the lamin molecule close to the ends of the a-helical domains. However, mutant lamins A lacking most of the carboxyl-terminal domain can still associate longitudinally to form fibrils [ 71. While initially it was assumed that phosphorylation of serines 22 and 392 destabilized the coiled-coil interactions between

and its cell cycle

Recent results suggest that the NL may be divided into three levels of organization, which appear to be maintained by interactions involving discrete parts of the lamin molecules [ 1,2**]. At the first level, two lamin polypeptides in a paralel unstaggered orientation interact via their central ahelical domains (type I interactions) to form dimers [ 1,2**,3,4.*]. Where this arrangement results in juxta posed cysteines, the dimers can be additionally stabilized by disuffide bonds resistant to mild reducing conditions [I], although it is doubtful that these bonds have biological significance, as not all lamin species contain cysteines

NE-nuclear

430

envelope;

NL-nuclear

lamina; @

Current

Abbreviations NPC-nuclear Biology

1992, 4:43&435

Ltd

pore 1SSN

complex; 0955-0674

MPF-maturation-promoting

factor.

Nuclear

lamins [5], there is now convincing evidence that mitotic phosporylation of lamins does not lead to dimer dissociation [ 1,2-1. This suggests that the changes induced by the phosphorylation of serines 22 and 392 are relatively localized and have little etfect on the a-helical parts of the molecules. The experimental evidence available to date is compatible with a model in which head-to-tail (type II> interactions are involved in organizing lamins as linear polymers. The latter are further crosslinked by dimerization, which adds further dimensions to the structure (Fig. 1). Such a model would not require all lamins to be dimerized, in agreement with experimental findings [ 11. The presence of at least two discrete types of interacting sites in the lamin molecule exampliIies a structural principle in which more than one type of saturatable interaction is required to build a two- or three-dimensional structure. Whether or not lamins can form heterodimers remains uncertain, although the answer might be provided by crosslinking experiments.

enveloDe

model of the nuclear lamina structure, in which monomeric lamin molecules form linear polymers (filaments) by head-to-tail interactions between their nonhelical aminoand carboxyl-terminal parts. These filaments are crosslinked into two- or three-dimensional structures by lamin dimerization. According to this model, all terminal interaction sites are occupied, while some lamin polypeptides could remain unpaired and interact with other nuclear envelope constituents via their helical domains.

In another important recent development, the identity of the lamin kinase has been established. It was shown, first in rlitro, and then in a homologous meiotic system, that during M-phase the lamins are phosphotylated by a complex containing the cdc2 kinase (~34~dC~) and cyclin B, known as the maturation-promoting factor [ 8,9001. These findings demonstrate that this factor, previously assumed to have a regulatory role, is directly involved in a specific mitotic reaction. Purified cdc2 kinase has also been shown to disassemble in l&-o reconstituted larnin Iilamen& and paracrystals, and to act as lamin kinase in fission yeast [ 2.0,4-,lO*]. The enzyme shows no species

Dessev

specificity: both cdc2 kinase purified from HeIa cells and the homologous enzyme are able to phosphorylate the single lamin of clam oocyte nuclei and to disassemble these nuclei [9oo]. Combined with similar observations from other laboratories [2**,4**], this suggests that the mechanism of the NE breakdown has been highly conserved during evolution. The initial results on NL disassembly established a seemingly simple sequence of events involving cdc2 kinase activation and lamin phosphorylation. However, further work may be expected to add more complexity to the sequence. For example, a recent experiment using microinjection of a specific inhibitor of CAMP-dependent protein kinase suggests that this enzyme may play a negative regulatory role in the initiation of mitosis and NE disassembly in mammalian cells [11*-l. The reversal of NE breakdown has been shown to involve lamin dephosphorylation [ 121. The protein phosphatases catalyzing this reaction have yet to be identified.

Association between the nuclear and the nuclear membrane

Fig. 1. A hypothetical

structure

lamina

Electron microscopy has revealed a close proximity between the NL and the nuclear membrane. During purification of the NE, the two structures behave as if physically associated with each other. The structural aspects of this association are not yet elucidated, but the location of the NL between the inner nuclear membrane and chromatin suggests that the lamins should interact with either one or both of these structures. Early studies have suggested that the inner nuclear membrane and the NL are connected through lamin B, since the latter remains attached to membrane vesicles after disassembly of the NE [13]. However, since no transmembrane domains have been found in the nuclear lamins, it appears more likely that the NL and the inner nuclear membrane interact indirectly via non-lamin components. Recently, the primary structure of one cardidate for this function, previously proposed to serve as a lamin B receptor, has been determined [ 14,151. The sequence has eight hydrophobic, potentially transmembrane domains, and two consensus sites for phosphorylation by protein kinase A, and may play a role in the regulation of lamin B binding [ 141. Another component of the nuclear envelope in chicken cells, a 54kD phosphoprotein, has been recently characterized and shown to be located at the inner nuclear membrane [ 16**]. This protein, which is also associated with the NL in a manner that depends on its phosphorylation by cdc2 kinase, is a potential candidate for an NL-bound membrane receptor [ 16**]. It is immunologically related to the previously described lamin B receptor but it remains to be established whether the two proteins are identical [14,15]. The results described so far are in agreement with earlier data from Burke and Get-ace [12] who showed that the formation of an NL polymer on the surface of chromatin in a cell-free system precedes, and is necessary for, the attachment of membrane vesicles [ 121.

431

432

Nucleus

ad

gene expression

. The concept that NL functions as a scaffold to the nuclear membrane, connecting it to chromatin, was recently challenged. Newport et al. [17-l showed that a nuclear membrane with pore complexes could form in vitro in the absence of lamins. Direct targeting of membrane vesicles to the chromatin surface in the absence of nuclear lamins has also been observed by Vigers and Lohka [18-l. These resnks suggest the possibility of a direct interaction between, ligands on the surface of chromatin and membrane-bound receptors in the process of reformation of the NL (Fig. 2). Furthermore, in zvh-o studies indicate that during mitosis this interaction is weakened by phosphotylation (perhaps involving cdc2 kinase), resulting in fragmentation of the nuclear membrane [19-l. A direct interaction between the nuclear membrane and chromatin has also been suggested by the earlier in ZOO observations of Stick and Schwartz [ 201, who found that although the NL disappears during some stages of meiosis, the nuclear membrane and NPC remain intact [ 201. A reconciliation of these two mechanisms was proposed in a recent review by Benavente [21*]. His microinjection experiments with anti-lamin antibodies demonstrated that the presence of the NL is necessaty for chromatin condensation and the formation of the nucleolus. Benavente suggests that early in NE refomlation, a minimal number of lamins associate with the chromatin surface to form a polymer. This is followed by assembly of membrane vesicles and NPC. Upon subsequent activation of the transport function of the NPC, more lamins are imported into the nucleus and form a continuous polymeric chromatin-organizing structure. Recent studies provide evidence that isoprenylation and carboxyl-methylation of the carboxyl-terminal Ras-like four-ammo-acid motif, C-a-a-X (where C is cysteine, a is an aliphatic ammo acid and X is any amino acid), found in both human lamin A and chicken lamin B, may also be necessary for the interaction between the lamins and elements of the inner nuclear membrane [22**,23]. These modifications may increase the hydrophobic nature of the carboxyl-terminal end of the molecule, which would then interact with the membrane, either directly or through receptors. All defined lamin sequences have nuclear location signals, and the components of the NL, as well as most of the intranuclear proteins, are thought to reach the nuclear interior through the central channel of the NPC. Recently, however, an alternative has been suggested for the transport of membrane proteins. Powell and Burke [24-l have found that a 55kD NE protein component (p55), previously described by Senior and Gerace [25], undergoes exchange between the nuclei of heterokaryons with a common endoplasmic reticulum. This exchange does not occur with nuclei of embryonic carcinoma cells that lack lamins A and C, but can be induced by transfecting the parent cells with lamin A before cell fusion. On the basis of these results, the authors propose a novel mechanism for targeting proteins to the inner nuclear membrane, which does not require a nuclear localization signal. Instead, a membrane protein (in this case ~55) is postulated to move by lateral diffusion from the endoplasmic reticulum to the outer and inner nu-

Cytoplasm Outer nuclear membrane

Inner nuclear membrane

Nuclear lamina

Nuclear pore

Receptor 1

1 Nucleus

Cytoplasm I

Nuclear oore

Inner nuclear membrane

Nuclear lamina

1

T L-Chromatin

Nucleus

I

Fig. 2. Alternative models for interactions between the nuclear envelope constituents and chromatin. (a) A receptor located on the Inner nuclear membrane interacts with chromatin-associated ligands, yet to be identified, at regions where the nuclear lamina (NL) is interrupted or absent. (b) A direct mode of interaction between the NL and chromatin. A protein constituent of the inner nuclear membrane (P), possibly functioning as lamin B receptor, is transported from the endoplasmic reticulum (ER) via the continuities between the outer and inner nuclear membranes, around the nuclear pore complex, to the inner membrane, where it accumulates by interacting with the NL. This process may be subject to specific restrictions, as the outer nuclear membrane contains protein markers that are absent from the inner nuclear membrane.

clear membranes via the continuous regions around the NPC. The protein then becomes fixed at the inner nuclear membrane by interaction with components of the NL, including lamins A and C (Fig. 2).

Association between the nuclear and cytoskeletal structures

envelope

Long-standing questions about the association of the NE with cytoskeletal elements still remain unresolved. Data continue to accumulate showing specific interactions between lamin B and cytoskeletal components ( [26] and references therein), although it is difficult to imagine

Nuclear

how they could be in physical contact as the NL and the cytoskeleton are separated by the double nuclear membrane and the perinuclear space. Further work, possibly including changes in our perception of the dynamic state of the NE, is needed to resolve this question.

functions

of the nuclear

structure

Dessev

chromatin which precludes a direct interaction with it [32]. These results suggest the existence of undiscovered functionally important molecules that connect the NL with chromatin.

Lamin Biological

envelope

evolution

envelope

The important role of the NPC in the traffic of macromolecules between nucleus and cytoplasm is treated separately in this issue (Davis pp 424-429). Here, 1 will deal with the possible role of the NE in chromatin structure and function. It has been assumed from indirect evidence that the NL is important for the structural organization of chromatin [27]. This hypothetical concept has been supported by a number of studies. DNA replication in reconstituted nuclei does not start before an intact NE is assembled around chromatin [28]. The NL appears to be particularly important, since membrane vesicles can bind to chromatin and fuse into a continuous layer containing NPC in the absence of lamins, but such nuclei can not replicate their DNA [17*-l. A similar effect is obsenled by Meier et al. [29-l, who demonstrate that nuclei as sembled in Xenopm extracts, functionally depleted of lamin III by binding to a monoclonal antibody, are unable to replicate their DNA, although chromatin condensation and formation of nuclear membranes with functional NPC occur normally. Microinjection of antilamin antibodies prevents chromatin condensation and the formation of nucleoli, as well as the normal transport functions of the NPC [21*]. All these findings clearly indicate that the NE is involved in some critical aspects of intranuclear organization. One possibility is that the NL is necessary for maintaining the integrity of an intranuclear structure, which is important for the assembly of the DNA replication apparatus. Ver)i little is known, however, about the association of the NL with the intranuclear matrix. A different aspect of NE function emerges from the work of Leno and Laskey [30-] who studied DNA replication in chicken erythroc-yte nuclei placed in Xetzoprts extracts. In this system, many individual demembranated nuclei formed aggregates enclosed in a common nuclear membrane. The individual nuclei within each agregate replicated their DNA synchronously, while different aggregates replicated out of .synchrony with each other, suggesting that the nuclear membrane selectively concentrates an essential replication factor(s) sufficient for only one round of replication [3I]. Unfortunately, the work contains no information on the state of the individual nuclear NL in a multinuclear aggregate. Until recently, the NL was believed to be a continuous layer closely associated with chromatin [ 271. However, surprising results from the Sedat laboratory [32] question both of these assumptions by showing that there are large regions in the nuclear envelope where no lamins can be detected. Furthermore, at places where NL filaments are present, they are located at a distance from

The nuclear lamins show extensive similarities in primary and secondary structures with the intermediate filament proteins, suggesting common origins (reviewed in [ 33) 1. Two recent studies [34,35] provide further insight into the evolutionary relationship of the lamins and intermediate filaments by describing the striking similarities between the intron patterns of their corresponding genes. On the basis of these data, it has been postulated that the intermediate filament proteins evolved from lamin ancestors by deletion of both the nuclear location signal and the C-terminal I&+-like C-a-a-X motif that is important for the association of the lamins with the nuclear membrane

134,351.

Conclusions The recent findings related to the NE have added a number of intriguing questions to the existing ones. In many cases interactions are suspected to occur, but what is the identity of the interacting molecules? In what way is the NE involved in chromatin structure and function? Are the developmental changes in NL composition biologically significant? Are there mechanisms of nucleo-cytoplasmic transport that bypass the nuclear pores? What are we likely to find in the perinuclear space? We have just begun to realize that an essential feature of the NJ! is its dynamics, not only during mitosis but also in interphase. It appears that the most exciting discoveries are still ahead and next year’s review in this series may present a more complete and perhaps surprisingly different picture of the nuclear envelope.

References

and recommended

Papers of particular interest, published \irn. have been highlighted ici: . of special interest .. of outstanding interest 1.

2. . .

within

reading the annual

period

of re-

DEWY G, lovc~~ev~-D~~sl’\’ C. G~LI)XWPI’ R: Lamin Dimers: Presence in the Nuclear Lamina of Surf Clam Oocytes and Release During Nuclear Envelope Breakdown. / Bio/ Cbem 1990. 265:1263G12641.

HE~TUNGEH E. PITTER M. H,WER M, Ltlsnc A. AEHI Ll, NIGG EA: Expression of Chicken Lamin B2 in Escherichiu coff Characterization of Its Structure, Assembly, and Molecular Interactions. J Cell Biol 1991. 113:4X5--195. Using a recombinant lamin expressed in bacteria, interaction between the Iamin molecules results in three distinct levels of structural organi.

7.3tion.

433

434

Nucleus 3.

and gene expression

Mom

RD,

DONAIDSON

cherichia and Tail Formation. 4. ..

AD,

STEWART

coU of Human Lamins Domains on Assembly J Cell Sci 1991,

PETER M, HEITUNGER

M:

Expiession

in

Es-

A and C: Influence of Head Properties and Paracrystal

99:363-372.

E, HANER

M. AEBI U,

NIGC

sembly of in u&o Formed Lamin Head-to-tail cdc2 Kinase. EMBO J 1991, 10:1535-1554.

EA

Disas-

Polymers

by

Using purified cdc2 kinase and recombinant chicken lamin B in vitro, the phosphotyiation of specific sites in the amino- and carboxy-termi. nal regions of the lamin molecules is shown to control their assembly and disassembly. 5.

HEALD R, MCKEON F: Mutations Lamin A that Prevents Nuclear tosis. Cell 1990, 61:579-589.

of Phosphorylation Lamina Disassembly

6.

WARLI GE, KIRSCHNER MW: Identification lated Phosphorylation Sites on Nuclear 61:561-577.

7.

GIEFFERS

C,

9. ..

PER Vitm

M,

of Cell Cycle-reguLamin C. Cell 1990.

NAKAGAWA

specific

Disassembly of Phosphorylation

1990,

61:591-

J. DOREE

the of

M,

LQ~BE JC,

Nuclear Lamins

Rethe

Lamina by cdc2

NIGG EA: In and M Phase-

Kinase.

Cell

DE%~EV G, IOVCHEVA-DESSEV

R: A Complex Containing lates the Nuclear Lamins

C. BISHOP:

JR, BEACH D, GOIDMAN

p3&Jc2 and Cyclin B Phosphoryand Disassembles Nuclei of Clam

10. ENOCH T, PETER M. NLIFISE P, NIGG EA: p34cdc2 Acts as a . Lamin Kinase in Fission Yeast. I Cell Biol 1991, 112:797*7. Chicken lamin B2 expressed in bacteria is incorporated into a structure that associates with the nucleus during interphase and is dispersed during mitosis. The resulb suggest the involvement of cdc2 kinase in this process. L+hm

NJC, CAVADORE JC. LABBE JC, MALIRER RA, FERNANDEZ

A:

Inhibition of cAMPdependent Protein Kinase Plays a Key Role in the Induction of Mitosis and Nuclear Envelope Breakdown in Mammalian Cells. EMBO J, 10:1523-1533.

Evidence is presented and discussed that cAMP-dependent protein kinase is critically involved, together with cdc2 kinase, in the regulation of cell cycle events such as nuclear envelope breakdown, chromosome condensation and microtubule reorganization. The resula suggest that the mechanism of control over mitotic events may be more complex than initially appeared. 12.

BURKE B, GERACE L A Cell-free

of the

Nuclear

Envelope

at the

System to Study End of Mitosis.

Reasembly Cell 1986.

44639-652. 13.

GERACE L, BOREL G: The

During 14.

Mitosis.

WORMAN

HJ. EVANS CD,

the Nuclear with Eight 1990, 15.

16. ..

Nuclear

Cell 1980,

Envelope Potential

Lamina

is Depolymerized

39~277-289.

B~QBEL G: The

Inner Membrane: Transmembrane

B Receptor of a Polytopic Protein

Lamin

Domains.

J Cell

BAIIIR

18.

..

SM, EPPENBERGER HM,

GRIFFITHS

G, NIGG

terization of a 54.kD Protein of the Inner Nuclear brane: Evidence for CeU Cycle Dependent Interaction the Nuclear Lamina J Cell Biol 1991, 114:398-400.

A 54.kD protein is characterized as an integral component nuclear membrane. It interacts with the NL in a manner phosphorylation by cdc2 kinase.

Memwith

of the inner affected by its

VIGERS GPA, Membranes

KL, DUNPHY WG: A Lamin-independent Envelope Assembly. J Cell Biol 1990,

LOHKA MJ: A Distinct

Vesicle Population and Pore Complexes to the Nuclear Eggs. J Cell Biol 1991, 112:54>556.

in Xenopus

..

Targets Envelope

R, S~MH~ C. NEWPORT JW: Assembly/Disassembly Nuclear Envelope Membrane: Cell Cycle-dependent Binding of Nuclear Membrane Vesicles to Chromatin Vitro. Cell 1’991, 65:20’+217. PFALIIR

of the

in

In rdro resultz indicate that the direct association between the inner nuclear membrane and chromatin is regulated by phosphorylation. 20.

STICK R. SCHWJART/. H: Disappearance

Nuclear Lamina Structure during in Oocytes. Ccl/ 1983, 33:94+958. 21. .

Analysed

22. ..

mN GT, prenylation,

23.

HOL’IZ

BENA\%NTE

R: Postmitotic in Living Cells.

and Reformation of the Specific Stages of Meiosis

Nuclear

Reorganization

Events

1991, 100:21>220. Summarizes antibody microinjection experiments showing that the formation of an NL structure is a prerequisite for chromatin condensation and nucleolus formation. In the absence of lamins, nuclear membrane and pore complexes are formed but are inactive in transporting kavophilic proteins into the nucleus; cells are arrested in telophase. ~~ro?m.so??fa

NICG EA: The CaaX Motif is Required for lsoCarboxyl Methylation, and Nuclear Membrane Association of Lamin B2. J Cell Biol 1991, 113:1323. This study shows that mutating the cysteine residue in the C-a.a-X carboxyl.tenninal motif to alanine abolishes both isoprenylation and carboxy methylation of the transfected lamin B2 and severely impairs its association with the nuclear membrane. This motif, when modiied, increases the hydrophobic&y of the carboxy-terminal domain. In lamin A, which does not associate with the membrane; the carboxyl terminus is proteolytically removed. D, TANAKA RA, HARI-WIG J, MCKEON

tif of Lamin A Functions in Conjunction Localization Signal to Target Assembly velope. Cell 1989, 59:96%977. 24. ..

Pou;r~u

L, BLI~KE B: Internuclear

F: The

with to the

Exchange

CaaX

Mo-

the Nuclear Nuclear En-

of an Inner

Nu-

clear Membrane Protein (~55) in Heterokaryons: in Vito Evidence for the Interaction of p55 with the Nuclear Lamina. J Cell Biol 1990, 111322252234.

An excellent study demonstrating exchange of a membrane protein between the nuclei of a heterokaryon by way of lateral diffusion following a pathnay from endoplasmic reticulum \ia outer and inner nuclear membranes. A novel mechanism of nucleo+zytoplasmic transport is proposed.

25.

A, GERACE L: Integral Membrane Proteins Inner Nuclear Membrane and Associated Lamina. J Cell Biol 1988, 107:2029-2036.

SENIOH

to the Nuclear

Biol

EA: Charac-

Nuclear

Nuclear envelope assembty requires soluble components in the cytosol and two distinct classes of vesicles, NEP-A and NEP-B. NEP-B vesicles bind chromatin, while NEP-A do not. ATP is not required for the binding of the vesicles to chromatin but is required for their fusion.

111:1535-1542.

WORKMAN HJ, J~IAN J, BARBEL G, GEORGATOS, SD: A Lamin B Receptor in the Nuclear Envelope. Proc NutI Acad Sci I!&4 1988, 85:8531-8534.

for

I 11:2247-2259. This study demonstrates that assembly of nuclear membranes containing pore complexes can occur in cell-free nuclear assembly extracts from frog eggs immunodepleted of lamin Llll. However, the presence of NL is needed for DNA synthesis to occur in assembled nuclei. This paper is important because it suggests that chromatin and the inner nuclear membnne may interact independently of the NL At the same time, the results indicate that the NL is important for the nuclear functions.

602.

Oocytes in Vitro. J Cell Biol 1991, 112:52$533. NL structures purified from clam -es are disassembled in r*i/ro by the cdc2-cyclin B complex isolated both from the same type of cells and from HeIa cell% In both cases the NL disassembly is accompanied by lamin phosphorylation at the same sites.

11. ..

NEWPORT JW, WUON

Pathway

19.

G: In vi&o Reconstitution of A and a Lamin A Mutant Lacking Tail. Eur J Cell Biol 1991, 55:191-199.

KROHNE

combinant Lamin Carboxy-terminal 8.

Sites in in Mi-

17.

..

26.

DJARALI K. PORII~% MM. SD: Network Antibodies

Physiological 27.

Cell 1991,

lCVI(COCK

R. BOUUI

Nuclear envelope structure.

The past 18 months have seen significant advances in our knowledge of the constituents of the nuclear envelope, their interactions during interphase a...
668KB Sizes 0 Downloads 0 Views