An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

REFERENCES

• Moir RD, Montag-Lowy M, Goldman RD. 1994. Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication. J. Cell Biol. 125:1201–1212. http://dx.doi.org/10.1083/jcb.125.6.1201.
   PubMed Web of Science ®Google Scholar
• Moir RD, Spann TP, Herrmann H, Goldman RD. 2000. Disruption of nuclear lamin organization blocks the elongation phase of DNA replication. J. Cell Biol. 149:1179–1192. http://dx.doi.org/10.1083/jcb.149.6.1179.
   PubMed Web of Science ®Google Scholar
• Ellis DJ, Jenkins H, Whitfield WG, Hutchison CJ. 1997. GST-lamin fusion proteins act as dominant negative mutants in Xenopus egg extract and reveal the function of the lamina in DNA replication. J. Cell Sci. 110:2507–2518.
   PubMed Web of Science ®Google Scholar
• Tsai MY, Wang S, Heidinger JM, Shumaker DK, Adam SA, Goldman RD, Zheng Y. 2006. A mitotic lamin B matrix induced by RanGTP required for spindle assembly. Science 311:1887–1893. http://dx.doi.org/10.1126/science.1122771.
   PubMed Web of Science ®Google Scholar
• Lopez-Soler RI, Moir RD, Spann TP, Stick R, Goldman RD. 2001. A role for nuclear lamins in nuclear envelope assembly. J. Cell Biol. 154:61–70. http://dx.doi.org/10.1083/jcb.200101025.
   PubMedGoogle Scholar
• Harborth J, Elbashir SM, Bechert K, Tuschl T, Weber K. 2001. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J. Cell Sci. 114:4557–4565.
   PubMed Web of Science ®Google Scholar
• Tang CW, Maya-Mendoza A, Martin C, Zeng K, Chen S, Feret D, Wilson SA, Jackson DA. 2008. The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. J. Cell Sci. 121:1014–1024. http://dx.doi.org/10.1242/jcs.020982.
   PubMedGoogle Scholar
• Belmont AS, Zhai Y, Thilenius A. 1993. Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. J. Cell Biol. 123:1671–1685. http://dx.doi.org/10.1083/jcb.123.6.1671.
   PubMed Web of Science ®Google Scholar
• Yang SH, Chang SY, Yin L, Tu Y, Hu Y, Yoshinaga Y, de Jong PJ, Fong LG, Young SG. 2011. An absence of both lamin B1 and lamin B2 in keratinocytes has no effect on cell proliferation or the development of skin and hair. Hum. Mol. Genet. 20:3537–3544. http://dx.doi.org/10.1093/hmg/ddr266.
   PubMed Web of Science ®Google Scholar
• Yang SH, Jung HJ, Coffinier C, Fong LG, Young SG. 2011. Are B-type lamins essential in all mammalian cells? Nucleus 2:562–569. http://dx.doi.org/10.4161/nucl.2.6.18085.
   PubMed Web of Science ®Google Scholar
• Kim Y, Zheng X, Zheng Y. 2013. Proliferation and differentiation of mouse embryonic stem cells lacking all lamins. Cell Res. 23:1420–1423. http://dx.doi.org/10.1038/cr.2013.118.
   PubMed Web of Science ®Google Scholar
• Davies BS, Coffinier C, Yang SH, Barnes RHII, Jung HJ, Young SG, Fong LG. 2011. Investigating the purpose of prelamin A processing. Nucleus 2:4–9. http://dx.doi.org/10.4161/nucl.2.1.13723.
   PubMed Web of Science ®Google Scholar
• Davies BS, Fong LG, Yang SH, Coffinier C, Young SG. 2009. The posttranslational processing of prelamin A and disease. Annu. Rev. Genomics Hum. Genet. 10:153–174. http://dx.doi.org/10.1146/annurev-genom-082908-150150.
   PubMed Web of Science ®Google Scholar
• Hennekes H, Nigg EA. 1994. The role of isoprenylation in membrane attachment of nuclear lamins. A single point mutation prevents proteolytic cleavage of the lamin A precursor and confers membrane binding properties. J Cell Sci. 107:1019–1029.
   PubMed Web of Science ®Google Scholar
• Krohne G, Waizenegger I, Hoger TH. 1989. The conserved carboxy-terminal cysteine of nuclear lamins is essential for lamin association with the nuclear envelope. J. Cell Biol. 109:2003–2011. http://dx.doi.org/10.1083/jcb.109.5.2003.
   PubMedGoogle Scholar
• Holtz D, Tanaka RA, Hartwig J, McKeon F. 1989. The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope. Cell 59:969–977. http://dx.doi.org/10.1016/0092-8674(89)90753-8.
   PubMed Web of Science ®Google Scholar
• Kitten GT, Nigg EA. 1991. The CaaX motif is required for isoprenylation, carboxyl methylation, and nuclear membrane association of lamin B2. J. Cell Biol. 113:13–23. http://dx.doi.org/10.1083/jcb.113.1.13.
   PubMed Web of Science ®Google Scholar
• Izumi M, Vaughan OA, Hutchison CJ, Gilbert DM. 2000. 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 11:4323–4337. http://dx.doi.org/10.1091/mbc.11.12.4323.
   PubMed Web of Science ®Google Scholar
• Bergo MO, Gavino B, Ross J, Schmidt WK, Hong C, Kendall LV, Mohr A, Meta M, Genant H, Jiang Y, Wisner ER, Van Bruggen N, Carano RA, Michaelis S, Griffey SM, Young SG. 2002. Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc. Natl. Acad. Sci. U. S. A. 99:13049–13054. http://dx.doi.org/10.1073/pnas.192460799.
   PubMed Web of Science ®Google Scholar
• Pendas AM, Zhou Z, Cadinanos J, Freije JM, Wang J, Hultenby K, Astudillo A, Wernerson A, Rodriguez F, Tryggvason K, Lopez-Otin C. 2002. Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nat. Genet. 31:94–99. http://dx.doi.org/10.1038/ng871.
   PubMed Web of Science ®Google Scholar
• Coffinier C, Jung HJ, Li Z, Nobumori C, Yun UJ, Farber EA, Davies BS, Weinstein MM, Yang SH, Lammerding J, Farahani JN, Bentolila LA, Fong LG, Young SG. 2010. Direct synthesis of lamin A, bypassing prelamin a processing, causes misshapen nuclei in fibroblasts but no detectable pathology in mice. J. Biol. Chem. 285:20818–20826. http://dx.doi.org/10.1074/jbc.M110.128835.
   PubMed Web of Science ®Google Scholar
• Geiger SK, Bar H, Ehlermann P, Walde S, Rutschow D, Zeller R, Ivandic BT, Zentgraf H, Katus HA, Herrmann H, Weichenhan D. 2008. Incomplete nonsense-mediated decay of mutant lamin A/C mRNA provokes dilated cardiomyopathy and ventricular tachycardia. J. Mol. Med. (Berl.) 86:281–289. http://dx.doi.org/10.1007/s00109-007-0275-1.
   PubMedGoogle Scholar
• Lillie RD, Ashburn LL. 1943. Supersaturated solutions of fat stains in dilute isopropanol for demonstration of acute fatty degeneration not shown by Herxheimer's technique. Arch. Pathol. 36:432–440.
   Google Scholar
• Lichti U, Anders J, Yuspa SH. 2008. Isolation and short-term culture of primary keratinocytes, hair follicle populations and dermal cells from newborn mice and keratinocytes from adult mice for in vitro analysis and for grafting to immunodeficient mice. Nat. Protoc. 3:799–810. http://dx.doi.org/10.1038/nprot.2008.50.
   PubMed Web of Science ®Google Scholar
• Koch PJ, de Viragh PA, Scharer E, Bundman D, Longley MA, Bickenbach J, Kawachi Y, Suga Y, Zhou Z, Huber M, Hohl D, Kartasova T, Jarnik M, Steven AC, Roop DR. 2000. Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. J. Cell Biol. 151:389–400. http://dx.doi.org/10.1083/jcb.151.2.389.
   PubMed Web of Science ®Google Scholar
• Jahn D, Schramm S, Schnolzer M, Heilmann CJ, de Koster CG, Schutz W, Benavente R, Alsheimer M. 2012. A truncated lamin A in the Lmna −/− mouse line: implications for the understanding of laminopathies. Nucleus 3:463–474. http://dx.doi.org/10.4161/nucl.21676.
   PubMed Web of Science ®Google Scholar
• Schmuth M, Martinz V, Janecke AR, Fauth C, Schossig A, Zschocke J, Gruber R. 2013. Inherited ichthyoses/generalized Mendelian disorders of cornification. Eur. J. Hum. Genet. 21:123–133. http://dx.doi.org/10.1038/ejhg.2012.121.
   PubMedGoogle Scholar
• Patterson JW. 2013. Practical skin pathology: a diagnostic approach. Elsevier/Saunders, Philadelphia, PA.
   Google Scholar
• Calonje E, McKee PH. 2012. McKee's pathology of the skin: with clinical correlations, 4th ed. Elsevier/Saunders, Edinburgh, United Kingdom.
   Google Scholar
• Radner FP, Grond S, Haemmerle G, Lass A, Zechner R. 2011. Fat in the skin: Triacylglycerol metabolism in keratinocytes and its role in the development of neutral lipid storage disease. Dermatoendocrinology 3:77–83. http://dx.doi.org/10.4161/derm.3.2.15472.
   PubMedGoogle Scholar
• Richard G. 2004. Molecular genetics of the ichthyoses. Am. J. Med. Genet. C Semin. Med Genet. 131C:32–44. http://dx.doi.org/10.1002/ajmg.c.30032.
   PubMedGoogle Scholar
• Elias PM, Williams ML, Holleran WM, Jiang YJ, Schmuth M. 2008. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J. Lipid Res. 49:697–714. http://dx.doi.org/10.1194/jlr.R800002-JLR200.
   PubMed Web of Science ®Google Scholar
• Radner FP, Streith IE, Schoiswohl G, Schweiger M, Kumari M, Eichmann TO, Rechberger G, Koefeler HC, Eder S, Schauer S, Theussl HC, Preiss-Landl K, Lass A, Zimmermann R, Hoefler G, Zechner R, Haemmerle G. 2010. Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58). J. Biol. Chem. 285:7300–7311. http://dx.doi.org/10.1074/jbc.M109.081877.
   PubMed Web of Science ®Google Scholar
• Lefevre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R, Lakhdar H, Wollenberg A, Verret JL, Weissenbach J, Ozguc M, Lathrop M, Prud'homme JF, Fischer J. 2001. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. Am. J. Hum. Genet. 69:1002–1012. http://dx.doi.org/10.1086/324121.
   PubMed Web of Science ®Google Scholar
• Shultz LD, Lyons BL, Burzenski LM, Gott B, Samuels R, Schweitzer PA, Dreger C, Herrmann H, Kalscheuer V, Olins AL, Olins DE, Sperling K, Hoffmann K. 2003. Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huet anomaly. Hum. Mol. Genet. 12:61–69. http://dx.doi.org/10.1093/hmg/ddg003.
   PubMed Web of Science ®Google Scholar
• Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima K, Stewart CL, Burke B. 1999. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147:913–920. http://dx.doi.org/10.1083/jcb.147.5.913.
   PubMed Web of Science ®Google Scholar
• Jung HJ, Nobumori C, Goulbourne CN, Tu Y, Lee JM, Tatar A, Wu D, Yoshinaga Y, de Jong PJ, Coffinier C, Fong LG, Young SG. 2013. Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration. Proc. Natl. Acad. Sci. U. S. A. 110:E1923–E1932. http://dx.doi.org/10.1073/pnas.1303916110.
   PubMed Web of Science ®Google Scholar
• Barrowman J, Hamblet C, George CM, Michaelis S. 2008. Analysis of prelamin A biogenesis reveals the nucleus to be a CaaX processing compartment. Mol. Biol. Cell. 19:5398–5408. http://dx.doi.org/10.1091/mbc.E08-07-0704.
   PubMed Web of Science ®Google Scholar
• Dwyer N, Blobel G. 1976. A modified procedure for the isolation of a pore complex-lamina fraction from rat liver nuclei. J. Cell Biol. 70:581–591. http://dx.doi.org/10.1083/jcb.70.3.581.
   PubMedGoogle Scholar
• Gerace L, Blum A, Blobel G. 1978. Immunocytochemical localization of the major polypeptides of the nuclear pore complex-lamina fraction. Interphase and mitotic distribution. J. Cell Biol. 79:546–566.
   PubMed Web of Science ®Google Scholar
• Fricker M, Hollinshead M, White N, Vaux D. 1997. Interphase nuclei of many mammalian cell types contain deep, dynamic, tubular membrane-bound invaginations of the nuclear envelope. J. Cell Biol. 136:531–544. http://dx.doi.org/10.1083/jcb.136.3.531.
   PubMed Web of Science ®Google Scholar
• Ellenberg J, Siggia ED, Moreira JE, Smith CL, Presley JF, Worman HJ, Lippincott-Schwartz J. 1997. Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis. J. Cell Biol. 138:1193–1206. http://dx.doi.org/10.1083/jcb.138.6.1193.
   PubMed Web of Science ®Google Scholar
• Akiyama M. 2011. Updated molecular genetics and pathogenesis of ichthiyoses. Nagoya J. Med. Sci. 73:79–90.
   PubMedGoogle Scholar
• Kalinin AE, Kajava AV, Steinert PM. 2002. Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioessays 24:789–800. http://dx.doi.org/10.1002/bies.10144.
   PubMed Web of Science ®Google Scholar
• Homberg M, Magin TM. 2014. Beyond expectations: novel insights into epidermal keratin function and regulation. Int. Rev. Cell. Mol. Biol. 311:265–306. http://dx.doi.org/10.1016/B978-0-12-800179-0.00007-6.
   PubMedGoogle Scholar
• Adeyo O, Allan BB, Barnes RHII, Goulbourne CN, Tatar A, Tu Y, Young LC, Weinstein MM, Tontonoz P, Fong LG, Beigneux AP, Young SG. 2014. Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice. J. Investig. Dermatol. 134:1589–1598. http://dx.doi.org/10.1038/jid.2014.19.
   PubMedGoogle Scholar
• Feingold KR. 2009. The outer frontier: the importance of lipid metabolism in the skin. J. Lipid Res. 50(Suppl):S417–S422. http://dx.doi.org/10.1194/jlr.R800039-JLR200.
   PubMed Web of Science ®Google Scholar
• Schmitz G, Muller G. 1991. Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. J. Lipid Res. 32:1539–1570.
   PubMed Web of Science ®Google Scholar
• Fartasch M. 2004. The epidermal lamellar body: a fascinating secretory organelle. J. Investig. Dermatol. 122:XI–XII. http://dx.doi.org/10.1111/j.0022-202X.2004.22541.x.
   PubMedGoogle Scholar
• Pappas A. 2009. Epidermal surface lipids. Dermatoendocrinology 1:72–76. http://dx.doi.org/10.4161/derm.1.2.7811.
   PubMedGoogle Scholar
• Waterham HR, Koster J, Mooyer P, Noort Gv G, Kelley RI, Wilcox WR, Wanders RJ, Hennekam RC, Oosterwijk JC. 2003. Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B receptor gene. Am. J. Hum. Genet. 72:1013–1017. http://dx.doi.org/10.1086/373938.
   PubMed Web of Science ®Google Scholar
• Olins AL, Rhodes G, Welch DB, Zwerger M, Olins DE. 2010. Lamin B receptor: multi-tasking at the nuclear envelope. Nucleus 1:53–70. http://dx.doi.org/10.4161/nucl.1.1.10515.
   PubMed Web of Science ®Google Scholar
• Wassif CA, Brownson KE, Sterner AL, Forlino A, Zerfas PM, Wilson WK, Starost MF, Porter FD. 2007. HEM dysplasia and ichthyosis are likely laminopathies and not due to 3beta-hydroxysterol Delta14-reductase deficiency. Hum. Mol. Genet. 16:1176–1187. http://dx.doi.org/10.1093/hmg/ddm065.
   PubMed Web of Science ®Google Scholar
• Coffinier C, Jung HJ, Nobumori C, Chang S, Tu Y, Barnes RHII, Yoshinaga Y, de Jong PJ, Vergnes L, Reue K, Fong LG, Young SG. 2011. Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons. Mol. Biol. Cell. 22:4683–4693. http://dx.doi.org/10.1091/mbc.E11-06-0504.
   PubMed Web of Science ®Google Scholar
• Potten CS, Saffhill R, Maibach HI. 1987. Measurement of the transit time for cells through the epidermis and stratum corneum of the mouse and guinea-pig. Cell Tissue Kinet. 20:461–472.
   PubMedGoogle Scholar
• Solecki DJ, Govek EE, Tomoda T, Hatten ME. 2006. Neuronal polarity in CNS development. Genes Dev. 20:2639–2647. http://dx.doi.org/10.1101/gad.1462506.
   PubMed Web of Science ®Google Scholar
• Tsai LH, Gleeson JG. 2005. Nucleokinesis in neuronal migration. Neuron 46:383–388. http://dx.doi.org/10.1016/j.neuron.2005.04.013.
   PubMed Web of Science ®Google Scholar
• Coffinier C, Chang SY, Nobumori C, Tu Y, Farber EA, Toth JI, Fong LG, Young SG. 2010. Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. Proc. Natl. Acad. Sci. U. S. A. 107:5076–5081. http://dx.doi.org/10.1073/pnas.0908790107.
   PubMed Web of Science ®Google Scholar
• Davies BS, Coffinier C, Yang SH, Jung HJ, Fong LG, Young SG. 2011. Posttranslational processing of nuclear lamins, p 21–41. In Tamanoi F, Hrycyna CA, Bergo MO (ed), The enzymes, vol 29. Elsevier, Amsterdam, The Netherlands.
   Google Scholar
• Young SG, Yang SH, Davies BS, Jung HJ, Fong LG. 2013. Targeting protein prenylation in progeria. Sci. Transl. Med. 5: 171ps173. http://dx.doi.org/10.1126/scitranslmed.3005229.
   Google Scholar