Nuclear Lamins

2024

Kim PA, Kim JR, Tu T, Jung H, Jeong JYB, Tran AP, Presnell A, Young SG*, and Fong LG*. (2024) Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina. Proc Natl Acad Sci USA. 121(27):e2406946121. doi: 10.1073/pnas.2406946121. PMID: 38917015. PMC11228511. *Co-senior and Co-corresponding authors
Kim PH, Kim JR, Heizer PJ, Jung H, Tu Y, Presnell A, Scheithauer J, Yu RG, Young SG, Fong LG. The accumulation of progerin underlies the loss of aortic smooth muscle cells in Hutchinson-Gilford progerin syndrome. (2024) bioRxiv [Preprint]. Nov 3:2024.10.29.620896. doi: 10.1101/2024.10.29.620896. PMID: 39554077

2023

Kim JR, Kim PH, Presnell A, Tu Y, Young SG. (2023). Revisiting the truncated lamin A produced by a commonly used strain of Lmna knockout mice.. Nucleus.14(1):2262308. doi: 10.1080/19491034.2023.2262308.

2021

Kim PH, Chen N, Heizer P, Tu Y, Yang Y, Weston TA, Gill NK, Rowat AC, Young SG, Fong LG. (2021) Nuclear membrane ruptures underlie the vascular pathology in a mouse model of Hutchinson-Gilford progeria syndrome. JCI Insight. 6(16): 151515. doi: 10.1172/jci.insight.151515.
Chen N, Kim PH, Tu Y, Yang Y, Heizer P, Young SG, Fong LG. (2021) Increased expression of LAP2β eliminates nuclear membrane ruptures in nuclear lamin-deficient neurons and fibroblasts. Proc. Natl. Acad. Sci USA. doi: 10.1073/pnas.2107770118.

2020

Chen N, Kim PH, Fong LG, Young SG. (2020) Nuclear membrane ruptures, cell death, and tissue damage in the setting of nuclear lamin deficiencies. Nucleus. 11(1): 237–249. doi: 10.1080/19491034.2020.1815410.
Heizer P, Yang Y, Tu Y, Kim PH, Chen NY, Hu Y, Yoshinaga Y, de Jong PJ, Vergnes L, Morales JE, Li RL, Jackson NJ, Reue K, Young SG, Fong LG. (2020) Deficiency in ZMPSTE24 and Resulting farnesyl-Prelamin A Accumulation Only Modestly Affect Mouse Adipose Tissue Stores. J Lipid Res. Jan 15. doi: 10.1194/jlr.RA119000593.

2019

Chen NY, Yang Y, Weston TA, Belling JN, Heizer P, Tu Y, Kim P, Edillo L, Jonas SJ, Weiss PS, Fong LG, Young SG. (2019) An Absence of Lamin B1 in Migrating Neurons Causes Nuclear Membrane Ruptures and Cell Death. Proc. Natl. Acad. Sci. USA Dec 17. doi: 10.1073/pnas.1917225116.
Gill NK, Ly C, Kim PH, Saunders CA, Fong LG, Young SG, Gant Luxton GW, Rowat AC. (2019) DYT1 dystonia patient-derived fibroblasts have increased deformability and susceptibility to damage by mechanical forces. Frontiers in Cell and Developmental Biology (in press).
Nmezi B, Xu J, Fu R, Arminger T, Bey G, Powell J, Ma H, Sullivan M, Tu Y, Chen N, Young SG, Stolz D, Dahl K, Liu Yang, Padiath Q. (2019) A concentric model predicts district roles for the A and B type lamins in the spatial organization and stability of the nuclear lamina. Proc. Natl. Acad. Sci. USA Feb 14. pii: 201810070. doi: 10.1073/pnas.1810070116. [Epub ahead of print]

2018

Kim PH, Luu J, Heizer P, Tu Y, Weston TA, Chen N, Lim C, Li RL, Lin PY, Dunn JCY, Hodzic D, Young SG, Fong LG. Disrupting the LINC complex in smooth muscle cells reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome. (2018) Sci Transl Med. 2018 Sep 26;10(460). pii: eaat7163. doi: 10.1126/scitranslmed.aat7163. PMC6166472
Chen NY, Kim P, Weston TA, Edillo L, Tu Y, Fong LG, Young SG. (2018) Fibroblasts lacking nuclear lamins do not have nuclear blebs or protrusions but nevertheless have frequent nuclear membrane ruptures. Proc. Natl. Acad. Sci USA 2018 Oct 2;115(40):10100-10105. doi: 10.1073/pnas.1812622115. Epub 2018 Sep 17. PMC6176609
Levy Y, Ross JA, Niglas M, Snetkov VA, Lynham S, Liao C-Y, Puckelwartz MJ, Hus, Y-M, Mcnally EM, Asheimer M, Harridge SDR, Young SG, Fong LG, Español Y, Lopez-Otin C, Kennedy BK, Lowe DA, Ochala J. (2018) Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness. JCI Insight 2018 Oct 4;3(19). pii: 120920. doi: 10.1172/jci.insight.120920. [Epub ahead of print]. PMC6237469.

2017

Gigante CM, Dibattista M, Dong FN, Zheng X, Yue S, Young SG, Reisert J, Zheng Y, Zhao H. (2017) Lamin B1 is required for mature neuron-specific gene expression during olfactory sensory neuron differentiation. Nat Commun. 8:15098. doi: 10.1038/ncomms15098. PMC5411488

2016

Razafsky D, Ward C, Potter C, Zhu W, Xue Y, Kefalov VJ, Fong LG, Young SG, Hodzic D. (2016) Lamin B1 and lamin B2 are long-lived proteins with distinct functions in retinal development. Mol Biol Cell. 27:1928–1937. PMC4907726
Lee JM, Nobumori C, Tu Y, Choi C, Yang SH, Jung HJ, Vickers TA, Rigo F, Bennett CF, Young SG, and Fong SG. (2016) Modulation of LMNA splicing as a strategy to treat prelamin A diseases. J. Clin. Invest. 126:1592–1602. PMC4811112

2015

Yang SH, Procaccia S, Jung JH, Tatar A, Tu Y, Bayguinov YR, Hwang SJ, Tran D, Ward SM, Fong LG, Young SG. (2015) Mice that express farnesylated versions of prelamin A in neurons develop achalasia. Hum Mol. Genet. 24:2826–2840. PMC4406294

2014

Jung H-J, Tu Y, Nobumori C, Yang SH, Herrmann H, Fong LG, and Young SG (2014) 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. Mol. Cell. Biol. 4:4534–4544. PMC4248738
Lee JM, Jung, H-J, Fong LG, and Young, SG. (2014) Do lamin B1 and lamin B2 have redundant functions? Nucleus 5:287–292. PMC4152341
Young, SG, Jung, H-J, Lee JM, and Fong LG. (2014) Nuclear lamins and neurobiology. Mol. Cell Biol. 34:2776–2785. PMC4135577
Lee JM, Tu Y, Tatar A, Wu D, Nobumori C, Jung HJ, Yoshinaga Y, Coffinier C, de Jong PJ, Fong LG, Young SG. (2014) Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2. Mol Biol Cell. 25:1666–1675. PMC4019497
Jung, H-J, Tu Y, Yang SH, Tatar A, Nobumori C, Wu D, Young SG, Fong LG. (2014) New Lmna knock-in mice provide a molecular mechanism for the 'segmental aging' in Hutchinson-Gilford progeria syndrome. Hum Mol. Genet. 23:1506–1515. PMC3929089

2013

Jung, H-J, 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. USA 110:E1923–32. PMC3666708
Young SG, Yang SH, Davies BS, Jung HJ, Fong LG. (2013) Targeting protein prenylation in progeria. Sci Transl Med. 6:171. PMC3725554
Jung H-E, Lee JM, Yang SH, Young SG, Fong LG. (2013). Nuclear lamins in the brain—new insights into function and regulation. Molec. Neurobiology 47:290–301. PMC3538886

2012

Chang SY, Farber E, Hudon SE, Yang SH, Adres DA, Spielmann HP, Hrycyna CA, Young SG, Fong LG. (2012) Inhibitors of protein geranylgeranyltransferase-I lead to prelamin A accumulation by inhibiting ZMPSTE24. J. Lipid Res. 53:1176-1182. PMC3351824
Young SG, Jung HJ, Coffinier C, Fong LG. (2012) Understanding the roles of nuclear A- and B-type lamins in brain development. J. Biol. Chem. 287:16103-16110. PMC3351360
Jung H-J, Coffinier C, Choe Y, Beigneux AP, Daveies BSF, Yang SH, Barnes RH, Hong J, Sun T, Pleasure SF, Young SG, Fong LG. (2012) Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. Proc. Natl. Acad. Sci USA 109:E423-31. PMC3289373

2011

Yang SH, Jung H-J, Coffinier C, Fong LG, Young SG. (2011) Are B-type lamins essential in all mammalian cells? Nucleus 2: 562–569. PMC3324344
Yang SH, Chang SY, Tu Y, Lawson GW, Bergo MO, Fong LG, Young SG. (2011) Severe hepatocellular disease in mice lacking one or both CaaX prenyltransferases. J. Lipid Res. 53:77–86. PMC3243483
Coffinier C, Jung HJ, Nobumori C, Chang S, Tu Y, Barnes RH 2nd, 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. 22:4683-93. PMC3226484
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 Genetics 20:3537–3544. PMC3159554
Davies BSJ, Coffinier C, Yang SH, Barnes RH, Jung HJ, Young SG, Fong LG. (2011) Investigating the purpose of prelamin A processing. Nucleus 2:4–9. PMC3104803

2010

Yang SH, Chang SY, Ren S, Wang Y, Andres DA, Spielmann HP, Fong LG, Young SG. (2010) Absence of progeria-like disease phenotypes in knock-in mice expressing a nonfarnesylated version of progerin. Hum Mol Genet. 20:436–444. PMC3016906
Coffinier C, Fong LG, Young SG. (2010) LINCing lamin B2 to neuronal migration: growing evidence for cell-specific roles of B-types lamin. Nucleus 1:407–411. PMC3027074
Davies BS, Barnes RH II, Tu Y, Ren S, Andres DA, Spielmann HP, Lammerding J, Wang Y, Young SG, Fong LG. (2010) An accumulation of nonfarnesylated prelamin A causes cardiomyopathy but not progeria. Hum. Mol. Genet. 19:2692–2694.
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. PMC2898298
Coffinier C, Chang SY, Nobumori C, Farber EA, Toth J, Fong LG, Young SG. (2010) Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. Proc. Natl. Acad. Sci. USA 107:5076–5081. PMC2841930
Yang SH, Andres DA, Speilmann HP, Young SG, Fong LG. (2010) Assessing the efficacy of protein farnesyltransferase inhibitors in mouse models of progeria. J. Lipid Res. 51:400–405. PMC2803242

2009

Lee R, Chang SY, Trinh H, White AC, Bergo MO, Fong LG, Lowry WE, Young SG. (2009) Genetic analysis of the importance of the protein prenyltransferases in skin keratinocytes. Hum. Molecular Gen. 19:1603–1617. PMC2846164
Worman HJ, Fong LG, Muchir A, Young SG. (2009) Laminopathies and the long strange trip from basic cell biology to therapy. J. Clin. Invest. 119:1825–1836. PMC2701866
Fong LG, Vickers TA, Farber EA, Choi C, Yun UJ, Hu Y, Yang SH, Coffinier C, Lee R, Yin L, Davies BS, Andres DA, Spielmann HP, Bennett CF, Young SG. (2009) Activating the synthesis of progerin, the mutant prelamin A in Hutchinson-Gilford progeria syndrome with antisense oligonucleotides. Hum. Mol. Genet. 18:2462–2471. PMC2694694
Davies BS, Fong LG, Yang SH, Coffinier C, Young SG. (2009) The posttranslational processing of prelamin A and disease. Ann. Rev. Genetics and Genomics 10:153–174. PMC2846822

2008

Davies BS, Yang SH, Farber E, Lee R, Buck SB, Andres DA, Spielmann HP, Agnew BJ, Tamanoi F, Fong LG, Young SG. (2008) Increasing the length of progerin's isoprenyl anchor does not worsen bone disease or survival in mice with Hutchinson-Gilford progeria syndrome. J. Lipid Res. 50:126–134. PMC3837462
Yang SH, Andres DA, Spielmann HP, Young SG, Fong LG. (2008) Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated. J. Clin. Invest. 118:3291–3300. PMC2525700
Coffinier C, Hudon SE, Lee R, Farber EA, Nobumori C, Miner JH, Andres DA, Spielmann HP, Hrycyna CA, Fong LG, Young SG. (2008) A potent HIV protease inhibitor, darunavir, does not inhibit ZMPSTE24 or lead to an accumulation of farnesyl-prelamin A in cells. J. Biol. Chem. 283:9797–9804. PMC2442292
Yang SH, Qiao X, Farber E, Chang SY, Fong LG, Young SG. (2008) Eliminating the synthesis of mature lamin A reduces phenotypes in mice carrying a Hutchinson-Gilford progeria syndrome allele. J. Biol. Chem. 283:7094–7099.

2007

Coffinier C, Hudon SE, Farber EA, Chang SY, Hrycyna CA, Young SG, Fong LG. (2007) From the Cover: HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells. Proc. Natl. Acad. Sci. USA 104:13432–13437. PMC1948915
Moulson CL, Fong LG, Gardner JM, Farber EA, Go G, Passariello A, Grange DK, Young SG, Miner JH. (2007) Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes. Hum Mutat. 28:882–889.
Ji JY, Lee RT, Vergnes L, Fong LG, Stewart CL, Reue K, Young SG, Zhang Q, Shanahan CM, Lammerding J. (2007) Cell nuclei spin in the absence of lamin B1. J. Biol. Chem. 282:20015–20026.

2006

Yang SH, Meta M, Qiao X, Frost D, Bauch J, Coffinier C, Majumdar S, Bergo MO, Young SG, Fong LF. (2006) A protein farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. J. Clin. Invest. 116:2115–2121. PMC2266774
Fong LG, Frost D, Meta M, Qiao X, Yang SH, Coffinier C, Young SG. (2006) A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science. 311:1621–1623.
Fong LG, Ng JK, Lammerding J, Vickers TA, Meta M, Coté N, Gavino B, Qiao X, Chang SY, Young SR, Yang SH, Stewart CL, Lee RT, Bennett CF, Bergo MO, Young SG. (2006) Prelamin A and lamin A appear to be dispensable: Implications for the treatment of progeria. J. Clin. Invest. 116:743–752. PMC1386109

2005

Young SG, Fong LG, Michaelis S. (2005) Prelamin A, Zmpste24, misshapen cell nuclei, and progeria—New evidence suggesting that protein farnesylation could be important for disease pathogenesis. J. Lipid Res. 46:2531–2558.
Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL, Miner JH, Young SG, Fong LG. (2005) Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc. Natl. Acad. Sci. USA 102:12873–12878. PMC1193538
Yang, S.H., Bergo, M.O., Toth, J.I., Qiao, X., Hu, Y., Sandoval, S., Meta, M., Bendale, P., Gelb, M.H., Young, S.G., and Fong, L.G. 2005. Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc Natl Acad Sci USA 102:10291-10296. PMC1174929
Michaelson D, Chieu VK, Bergo M, Siletti J, Young S, and Philips M. (2005) Post-prenylation CAAX processing is required for farnesylated but not gernaylgeranylated GTPases. Molec. Biol. Cell 16:1606–1616.

2004

Fong LG, Ng JK, Meta M, Coté N, Yang SH, Burghardt A, Majumdar S, Reue K, Bergo MO, Young SG. (2004) Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc. Natl. Acad. Sci. USA 101:18111–18116. PMC536056

2002

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. USA 99:13049–13054. PMC130584

2001

Leung GK, Schmidt WK, Bergo MO, Gavino B, Wong DH, Tam A, Ashby MN, Michaelis S, Young SG. (2001) Biochemical studies of Zmpste24-deficient mice. J. Biol. Chem. 276:29051–29058.