Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003 May 15;423(6937):293-8. PubMed.
Recommends
Please login to recommend the paper.
Comments
University of Maryland, Baltimore
Lamin Mutation in Progeria: Is Premature Aging a Cytoskeletal Disease?
Two papers published online in Science (1) and Nature (2) describe the remarkable news that Hutchinson-Gilford Progeria Syndrome (HGPS), a disease characterized by premature aging, is associated with mutations in the human lamin A/C gene. These papers not only open the door to a better, molecular understanding of what goes wrong in these exceedingly rare disorders, but also point to the importance of the cytoskeleton, particularly the nuclear meshwork of intermediate filaments, in the aging process. They also suggest a new angle that could be investigated in neurodegenerative diseases.
Progeria is Greek for "prematurely old." The disease derives its name from the two people who first described the syndrome: Jonathan Hutchinson in 1886 and Hastings Gilford in 1904. HGPS occurs in one in every eight million live births. Affected children share characteristic features, including a small face and jaw relative to head size and many early signs of aging, such as baldness, generalized atherosclerosis, cardiovascular problems, aging of the skin, and frequent bone fractures. Median survival is only 13.4 years.
Up to now, the cause of this disease was unknown. The two reports arrive at the same conclusion that mutations in the lamin A/C gene, which encodes the nuclear proteins lamin A and C, are linked to many, if not most, cases of HGPS.
Lamin proteins belong to the intermediate filament (IF) family of cytoskeleton proteins. At 10 nm in diameter, IFs are in between actin filaments (6-7 nm) and microtubules (25 nm) in size, but unlike these, IFs have no known polarity. Moreover, IFs are assembled from subunits that are very heterogeneous in sequence. The IF proteins have been grouped into five classes, I-V, based on sequence homology, gene organization, and expression patterns (3,4). Class I comprises basic keratins; class II comprises acidic keratins; class III comprises desmin, vimentin, glial fibrillary acidic protein (GFAP), peripherin, and nestin; class IV comprises α-internexin and the neurofilament triplet proteins NF-L, NF-M, and NF-H; and class V comprises type A and type B lamins. All these proteins form filaments in the cytoplasm, except the lamins, which are found only in the nucleus.
All IF protein subunits share the same tripartite organization: a central, highly conserved α-helical rod domain flanked by variable head and tail domains. The rod domain in cytoplasmic IF proteins is 310 residues long, whereas in lamins it is 352 residues long, thanks to an insertion of a 42-amino acid (aa) sequence with α-helical properties (5,6). Interestingly, the 42-aa insertion is also present in IF proteins from invertebrates (7,8), leading to the suggestion that vertebrate lamin proteins were the precursors of vertebrate cytoplasmic IF proteins, which lost the 42-aa segment during evolution. Apart from their longer rod domains, lamins differ from cytoplasmic IF proteins by containing a nuclear localization signal (NLS) in their tail domains and a CAAX motif (C, cysteine; A, any aliphatic amino acid; X, any amino acid) at the C-terminus of many, but not all lamin proteins. The NLS functions in the transport of proteins to the nucleus, whereas the CAAX motif serves as the signal for a complex series of hydrophobic modifications involving isoprenylation and carboxymethylation of the cysteine residue and proteolytic cleavage of the C-terminal AAX residues. The hydrophobic modifications associated with the CAAX motif facilitate attachment of the lamin proteins to the nuclear membrane 9.
Structural studies have shown that IF assembly is driven chiefly by coiled-coil interactions of the rod domain of IF subunits, and that the head and tail domains also play important roles in lateral association and stabilization of higher-order filament structures (3).
Although IFs were originally considered to provide merely an inert, structural framework for cells, they are now recognized as dynamic structures that change rapidly in response to external and internal cellular conditions. Perhaps the most telling clue about the importance of IF proteins in cells and animals lies in the spectrum of human diseases associated with mutations in IF genes. Mutations in keratins are associated with a variety of different human skin disorders (10,11); mutations in desmin are tied to muscle and cardiac myopathies (12,13); mutations in GFAP are linked with the neurodegenerative Alexander disease (14); mutations in peripherin link to retinitis pigmentosa (15); mutations in neurofilament genes are associated with amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (16,17); and mutations in lamins are linked to Emery-Dreifuss muscular dystrophy, cardiomyopathy, and partial lipodystrophy (18,19). Many of the disease-associated mutations in IF genes map to the rod domain of their respective proteins, which is known to be important for stabilizing protein-protein interactions between subunits in filaments and their associated complexes (20). Interestingly, the mutations in the lamin A/C gene linked to HGPS map to the C-terminal end of the lamin A protein (1,2).
Lamin proteins occur as an orthogonal filament meshwork just beneath the nuclear envelope (21,22,23). This network has been detected in Xenopus nuclei; the assembly structure of these proteins in mammalian cells is unclear. Lamin proteins are believed to anchor nuclear pores as well as provide a bridge that links DNA to the nuclear envelope. Results of immunodepletion and nuclear reconstitution studies have indicated that lamin proteins might not be essential for nuclear envelope reassembly, but are required for further growth of the nuclear envelope and for DNA replication and gene transcription (24-28).
Lamin proteins fall into two groups on the basis of their solubility at mitosis: A-type lamins become soluble at mitosis, whereas B-type lamins remain insoluble (29). Human B-type lamins are composed of lamins B1 and B2, which derive from separate genes. B-type lamins are expressed in all germ and somatic cells. By contrast, A-type lamins in humans are composed of the major lamins A and C proteins, plus some minor polypeptides that are all generated by the alternative splicing of transcripts produced from a single 12 exon-containing lamin A/C gene on chromosome 1. Human lamin A (664 aa) differs from lamin C (572 aa) by containing 98 unique C-terminal residues, whereas lamin C differs from lamin A by possessing six unique residues at its C-terminus.
Lamins A and C are not expressed in embryonic cells; their expression appears to be turned on later during development coinciding with cell differentiation. Studies have suggested that A-type lamins may be required for chromatin remodeling and expression of specific sets of genes required for differentiation (30).
Gene knockout studies indicate that lamin A/C-/- mice develop to term, but display severe growth retardation and acute symptoms consistent with general muscular dystrophy; they die two months after birth (31). RNA interference (RNAi) studies have indicated that lamin B, but not A and C, is essential for the survival of tissue culture cells (32).
In the Science paper, De Sandre-Giovannoli et al. (1) describe two HGPS patients who have a heterozygous C to T transition at nucleotide 1824 of the lamin A open-reading frame. The mutation did not alter the amino acid encoded at that position (residue 608), but generated a cryptic donor splice site that the transcription machinery used to produce a truncated lamin A protein deleted of an internal 50 amino acid sequence at the C-terminal end of the protein. Remarkably, Eriksson et al. (2) found that 19 out of 23 HGPS children in their study also contained a base substitution in codon 608 of lamin A. They, too, found that most of the mutations generated polypeptides that deleted 50 amino acids in the C-terminal tail of the protein. These mutations were absent in the parents of eight cases for which DNA was available, indicating that they arise de novo. Why codon 608 of lamin A is particularly vulnerable to such spontaneous mutations is unknown. Though lamin C is produced from the same gene as lamin A, the HGPS mutations occur after the stop codon in lamin C and, therefore, do not affect that protein.
De Sandre-Giovannoli used a panel of lamin antibodies for immunofluorescence staining of lymphocytes from one patient; one antibody recognized both lamin A and C proteins, one was specific for lamin A, and one for lamin B1. This revealed nuclear rim staining, no staining, and mislocalization of lamin B1 to the nucleoplasm, respectively, suggesting abnormal expression and localization of lamin proteins in these cells. In culture, these lymphocytes had numerous cytoplasmic vacuoles and irregularities in mitotic figures. The cells’ nuclei had abnormal sizes and shapes, the nuclear envelopes were broken in places, and DNA had extruded into the cytoplasm. Eriksson et al. (2) also demonstrated that fibroblasts cultured from HGPS patients were abnormally shaped, with their nuclei looking more like cauliflower rather than being smooth. These findings imply that that expression of the deleted lamin A protein, and/or the loss of normal lamin A, causes abnormalities in nuclear shape and structure, which is somehow linked to development of this disease.
The question, then, is: How exactly do alterations in lamin A protein cause disease? The simplest possibility is that the mutant lamin A protein malfunctions because the 50 amino acid deletion removes the endoproteolytic cleavage site required for maturation of lamin A protein. Curiously, lamin A is initially synthesized as a precursor protein with its C-terminal CAAX motif, which is rapidly modified by isoprenylation. After its incorporation into the lamina, prelamin A is endoproteolytically cleaved so that the 15 C-terminal residues (18 residues in all, when one adds the three amino acids removed previously during isoprenylation) and any associated CAAX modifications are removed (33). It is interesting to note that isoprenylation is required for endoproteolysis of lamin A, suggesting that cleavage occurs at the membrane (34). Consequently, mature lamin A, like lamin C, is devoid of any CAAX modifications. Previous studies have shown that mature lamin A can be reincorporated into the lamina during progressive cell cycles (29,35). By contrast, lamin B proteins always retain their CAAX-associated modifications because those proteins are not proteolytically processed. The inability of mutant lamin A proteins in HGPS to be endoproteolytically cleaved at the correct time might affect the normal dynamics of lamin protein assembly at the nuclear lamina. For example, after initial targeting to the nuclear envelope, cleavage of lamin A’s C-terminal sequences might be necessary for proper function or assembly of the protein at nuclear lamina.
Interestingly, Lutz et al. (36) had demonstrated that a lamin A mutant deleted of 21 C-terminal residues was efficiently incorporated into the nuclear lamina, whereas a nonprenylated wild-type form of lamin A protein was defective in assembly, suggesting that deletion of the C-terminal end of lamin A removes a sequence that normally blocks assembly of prelamin A to the lamina. Thus, a lamin A protein with and without its CAAX-associated modification might behave differently in cells. There is considerable information about the in vivo targeting and assembly of recombinant lamin proteins with or without a CAAX motif. Several groups, including ours, have demonstrated that localization and targeting of human lamins differs depending on whether the proteins contain this motif (36-39). The main conclusion of these studies was that CAAX-associated modifications enable the rapid targeting of lamin proteins to the nuclear envelope, presumably facilitating their correct assembly both in time and space (36,38,40). By contrast, when the CAAX motif is deleted from human lamin A or B proteins, the mutant proteins accumulate within aggregates in transfected cell nuclei early after transfection, but over time, the proteins eventually are targeted to the lamina. Lamin C, which lacks a CAAX motif, also accumulates in aggregates in cells early after overexpression, but it, too, redistributes to the lamina over time. Nuclear aggregates formed by lamins A, B, and C proteins lacking the CAAX motif are quite different both in size and number (34) suggesting that either the proteins accumulate at different sites in the nucleus, or that they form different types of aggregates.
Other evidence suggests that incorporation of lamin C at the lamina may be dependent on lamin A expression (41,42). Thus, lamin A mislocalization in HGPS might cause defects in lamin C localization. Unfortunately, neither of the two papers provide information about the cellular localization of the mutant, truncated lamin A protein or lamin C in cells of HGPS patients, presumably for lack of antibodies specific for the six C-terminal residues of the lamin C protein. Instead, both groups used an anti-lamin antibody that would have cross-reacted with either wild-type lamin A, the truncated lamin A protein, or lamin C, leaving uncertain as to which of the three proteins was detected in the cells. De Sandre-Giovannoli et al. show that cells from an HGPS patient lacked anti-lamin A staining with an antibody specific to the C-terminus of lamin A; this suggests that wild-type lamin A protein generated from the unaffected lamin A allele does not accumulate in the affected cells.
Alternatively, deletion of the 50-aa sequence in the tail of lamin A might have removed an important functional site in the protein apart from that involved in assembly. (The two are not mutually exclusive.) Eriksson et al. (2) point out that a phosphorylation site is removed by the deletion, which might be important for the function of the protein. It is also possible that the presence of mutant lamin A protein, or the loss of normal lamin A proteins from the affected cells, compromises proper targeting of lamin proteins themselves and/or of their binding partners. Interestingly, De Sandre-Giovannoli et al. demonstrate that in cells of an HGPS patient, localization of lamin B1 was altered from its normal nuclear envelope site to more interior regions of the nucleus. However, it was unclear whether the mislocalized lamin B1 protein had lost its CAAX-associated modifications, or whether the protein was still attached to misplaced remnants of the nuclear envelope.
It is curious that De Sandre-Giovannoli et al. found lamin B1 protein to be mislocalized in cells of a HGPS patient, considering that proper targeting of this protein does not normally depend on lamin A or C proteins (41,42). This observation suggests that expression of the mutant lamin A protein in HGPS might have triggered the disassembly of the lamin B1 protein. Alternatively, when lamin A and C are expressed together in cells, the ratio of the two proteins to one another or to other lamin proteins could be critical, such that an imbalance in expression of one lamin could trigger mislocalization of another. Both groups show tantalizing evidence suggesting that the normal ratio of lamin A and C proteins might be different in HGPS cells.
A final possibility for why a mutation in lamin A protein causes HGPS is that certain cell types might require expression of a particular set of lamin proteins, and that loss of one of these lamin proteins could compromise the function of that cell. Knowledge of the expression and localization of lamin proteins in other cell types of HGPS patients might be illuminating in this regard.
The damage seen at the nuclear envelope in HGPS patients leading to extrusion of DNA into the cytoplasm is particularly intriguing because it suggests that nuclei of the affected cells are fragile. This could be because the lamina cytoskeleton that normally anchors the nuclear envelope appears to be compromised in these cells. The most straightforward reason for this underlying defect is that loss of lamin assembly leads to malformation of the cytoskeleton cage. Whether such a defect really exists might be difficult to visualize in the electron microscope due to technical difficulties that have, so far, prevented visualization of this structure in mammalian cells. Loss of the lamin cytoskeleton might also compromise DNA replication, or transcription of certain genes, since both processes have been linked to lamin proteins (18,23,28).
The other intriguing finding seen in cells from HGPS-affected individuals concerned abnormalities in the mitotic figures. Although details of the precise abnormalities were not provided, the defects might be related to the known chromosome-binding properties of lamin proteins (43,44). Abnormally located lamin proteins in cells of HGPS patients might bind proteins important for proper segregation of chromosomes, or they might bind at inappropriate times to chromosomes and cause their missegregation.
Clearly the new findings open up exciting avenues for further investigation into the underlying mechanisms of HGPS. The serendipitous finding that lamin proteins are associated with this disease provide an impetus for understanding the role of these IF proteins in controlling cell shape, structure, and function. Future studies will surely scrutinize exactly how the mutations affect lamin assembly and, consequently, nuclear and cell function.
The discovery of lamin A as a new gene involved in aging highlights why a basic understanding of the function of different proteins can be illuminating in unexpected ways. The new findings will undoubtedly spur research into the role of nuclear IF proteins in normal cell function, during aging, and in disease. This understanding will provide much-needed information of how nuclear architecture can influence nuclear function and consequently the role of the nucleus during aging.
Finally, the new evidence showing that mutations in lamin proteins are involved in premature aging reinforces, once again, the importance of the cytoskeleton in normal cell function and the aging process. It will be interesting to examine brains of people with HGPS to see if they contain any neuropathologic lesions that might link this disease to an of the many different age-related neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases or amyotrophic lateral sclerosis. The notion that defects in the cytoskeleton could be involved in age-related neurodegenerative diseases, as well, is not new, as defects in microtubules and neurofilaments have been linked for some time to Alzheimer’s, frontotemporal dementia, and ALS. Surely there remains little doubt, given these new findings, of the importance of the cytoskeleton in aging. One wonders how many other defects in the cytoskeleton, particularly in the nuclear cytoskeleton, are involved in the etiology of other aging diseases.
(I would like to thank Maria Eriksson, Gabrielle Strobel, and Ann Pluta for critical comments and suggestions. I apologize for omitting many other key articles; citing them all would have gone beyond the scope of this comment.)
References:
De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Lévy N. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003 Jun 27;300(5628):2055. PubMed.
Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003 May 15;423(6937):293-8. PubMed.
Herrmann H, Aebi U. Intermediate filaments and their associates: multi-talented structural elements specifying cytoarchitecture and cytodynamics. Curr Opin Cell Biol. 2000 Feb;12(1):79-90. PubMed.
Stewart M. Intermediate filaments: structure, assembly and molecular interactions. Curr Opin Cell Biol. 1990 Feb;2(1):91-100. PubMed.
Parry DA, Conway JF, Steinert PM. Structural studies on lamin. Similarities and differences between lamin and intermediate-filament proteins. Biochem J. 1986 Aug 15;238(1):305-8. PubMed.
Monteiro MJ, Hicks C, Gu L, Janicki S. Determinants for intracellular sorting of cytoplasmic and nuclear intermediate filaments. J Cell Biol. 1994 Dec;127(5):1327-43. PubMed.
Weber K, Plessmann U, Ulrich W. Cytoplasmic intermediate filament proteins of invertebrates are closer to nuclear lamins than are vertebrate intermediate filament proteins; sequence characterization of two muscle proteins of a nematode. EMBO J. 1989 Nov;8(11):3221-7. PubMed.
Zimek A, Weber K. The gene for a cytoplasmic intermediate filament (IF) protein of the hemichordate Saccoglossus kowalevskii; definition of the unique features of chordate IF proteins. Gene. 2002 Apr 17;288(1-2):187-93. PubMed.
Nigg EA, Kitten GT, Vorburger K. Targeting lamin proteins to the nuclear envelope: the role of CaaX box modifications. Biochem Soc Trans. 1992 May;20(2):500-4. PubMed.
Fuchs E. Keratins and the skin. Annu Rev Cell Dev Biol. 1995;11:123-53. PubMed.
Irvine AD, McLean WH. Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation. Br J Dermatol. 1999 May;140(5):815-28. PubMed.
Carlsson L, Thornell LE. Desmin-related myopathies in mice and man. Acta Physiol Scand. 2001 Mar;171(3):341-8. PubMed.
Goudeau B, Dagvadorj A, Rodrigues-Lima F, Nédellec P, Casteras-Simon M, Perret E, Langlois S, Goldfarb L, Vicart P. Structural and functional analysis of a new desmin variant causing desmin-related myopathy. Hum Mutat. 2001 Nov;18(5):388-96. PubMed.
Johnson AB. Alexander disease: a review and the gene. Int J Dev Neurosci. 2002 Jun-Aug;20(3-5):391-4. PubMed.
Loewen CJ, Moritz OL, Molday RS. Molecular characterization of peripherin-2 and rom-1 mutants responsible for digenic retinitis pigmentosa. J Biol Chem. 2001 Jun 22;276(25):22388-96. PubMed.
Julien JP. Neurofilament functions in health and disease. Curr Opin Neurobiol. 1999 Oct;9(5):554-60. PubMed.
Brownlees J, Ackerley S, Grierson AJ, Jacobsen NJ, Shea K, Anderton BH, Leigh PN, Shaw CE, Miller CC. Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum Mol Genet. 2002 Nov 1;11(23):2837-44. PubMed.
Worman HJ, Courvalin JC. The nuclear lamina and inherited disease. Trends Cell Biol. 2002 Dec;12(12):591-8. PubMed.
Hutchison CJ, Alvarez-Reyes M, Vaughan OA. Lamins in disease: why do ubiquitously expressed nuclear envelope proteins give rise to tissue-specific disease phenotypes?. J Cell Sci. 2001 Jan;114(Pt 1):9-19. PubMed.
Stewart M. Intermediate filament structure and assembly. Curr Opin Cell Biol. 1993 Feb;5(1):3-11. PubMed.
Aebi U, Cohn J, Buhle L, Gerace L. The nuclear lamina is a meshwork of intermediate-type filaments. Nature. 1986 Oct 9-15;323(6088):560-4. PubMed.
Hutchison CJ, Bridger JM, Cox LS, Kill IR. Weaving a pattern from disparate threads: lamin function in nuclear assembly and DNA replication. J Cell Sci. 1994 Dec;107 ( Pt 12):3259-69. PubMed.
Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK, Spann TP. Nuclear lamins: building blocks of nuclear architecture. Genes Dev. 2002 Mar 1;16(5):533-47. PubMed.
Newport JW, Wilson KL, Dunphy WG. A lamin-independent pathway for nuclear envelope assembly. J Cell Biol. 1990 Dec;111(6 Pt 1):2247-59. PubMed.
Meier J, Campbell KH, Ford CC, Stick R, Hutchison CJ. The role of lamin LIII in nuclear assembly and DNA replication, in cell-free extracts of Xenopus eggs. J Cell Sci. 1991 Mar;98 ( Pt 3):271-9. PubMed.
Lopez-Soler RI, Moir RD, Spann TP, Stick R, Goldman RD. A role for nuclear lamins in nuclear envelope assembly. J Cell Biol. 2001 Jul 9;154(1):61-70. PubMed.
Moir RD, Spann TP. The structure and function of nuclear lamins: implications for disease. Cell Mol Life Sci. 2001 Nov;58(12-13):1748-57. PubMed.
Hutchison CJ. Lamins: building blocks or regulators of gene expression?. Nat Rev Mol Cell Biol. 2002 Nov;3(11):848-58. PubMed.
Gerace L, Blobel G. The nuclear envelope lamina is reversibly depolymerized during mitosis. Cell. 1980 Jan;19(1):277-87. PubMed.
Burke B, Stewart CL. Life at the edge: the nuclear envelope and human disease. Nat Rev Mol Cell Biol. 2002 Aug;3(8):575-85. PubMed.
Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima K, Stewart CL, Burke B. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol. 1999 Nov 29;147(5):913-20. PubMed.
Harborth J, Elbashir SM, Bechert K, Tuschl T, Weber K. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci. 2001 Dec;114(Pt 24):4557-65. PubMed.
Weber K, Plessmann U, Traub P. Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina. FEBS Lett. 1989 Nov 6;257(2):411-4. PubMed.
Beck LA, Hosick TJ, Sinensky M. Isoprenylation is required for the processing of the lamin A precursor. J Cell Biol. 1990 May;110(5):1489-99. PubMed.
Gerace L, Blum A, Blobel G. Immunocytochemical localization of the major polypeptides of the nuclear pore complex-lamina fraction. Interphase and mitotic distribution. J Cell Biol. 1978 Nov;79(2 Pt 1):546-66. PubMed.
Lutz RJ, Trujillo MA, Denham KS, Wenger L, Sinensky M. Nucleoplasmic localization of prelamin A: implications for prenylation-dependent lamin A assembly into the nuclear lamina. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3000-4. PubMed.
Holtz D, Tanaka RA, Hartwig J, McKeon F. The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope. Cell. 1989 Dec 22;59(6):969-77. PubMed.
Mical TI, Monteiro MJ. The role of sequences unique to nuclear intermediate filaments in the targeting and assembly of human lamin B: evidence for lack of interaction of lamin B with its putative receptor. J Cell Sci. 1998 Dec;111 ( Pt 23):3471-85. PubMed.
Izumi M, Vaughan OA, Hutchison CJ, Gilbert DM. Head and/or CaaX domain deletions of lamin proteins disrupt preformed lamin A and C but not lamin B structure in mammalian cells. Mol Biol Cell. 2000 Dec;11(12):4323-37. PubMed.
Sasseville AM, Raymond Y. Lamin A precursor is localized to intranuclear foci. J Cell Sci. 1995 Jan;108 ( Pt 1):273-85. PubMed.
Pugh GE, Coates PJ, Lane EB, Raymond Y, Quinlan RA. Distinct nuclear assembly pathways for lamins A and C lead to their increase during quiescence in Swiss 3T3 cells. J Cell Sci. 1997 Oct;110 ( Pt 19):2483-93. PubMed.
Vaughan A, Alvarez-Reyes M, Bridger JM, Broers JL, Ramaekers FC, Wehnert M, Morris GE, Whitfield WGF, Hutchison CJ. Both emerin and lamin C depend on lamin A for localization at the nuclear envelope. J Cell Sci. 2001 Jul;114(Pt 14):2577-90. PubMed.
Glass JR, Gerace L. Lamins A and C bind and assemble at the surface of mitotic chromosomes. J Cell Biol. 1990 Sep;111(3):1047-57. PubMed.
Burke B. On the cell-free association of lamins A and C with metaphase chromosomes. Exp Cell Res. 1990 Jan;186(1):169-76. PubMed.
Make a Comment
To make a comment you must login or register.