The Autophagic Protein LC3 Translocates to the Nucleus and Localizes in the Nucleolus Associated to NUFIP1 in Response to Cyclic Mechanical Stress

Overview

Journal Autophagy

Specialty Cell Biology

Date 2019 Sep 4

PMID 31476975

Citations 34

Authors

Myoung Sup Shim

April Nettesheim

Joshua Hirt

Paloma B Liton

Affiliations

Soon will be listed here.

Abstract

Abbreviation: AdGFP: adenovirus encoding GFP; ATG: autophagy-related; BSA: bovine serum albumin; CMS: cyclic mechanical stretch; Co-IP: coimmunoprecipitation; DAPI: 4',6-diamidino-2-phenylindole; DFCs: dense fibrillar components; EM: electron microscopy; FCs: fibrillar centers; GCs: granular components; GFP: green fluorescent protein; hTM: human trabecular meshwork; HBSS: Hanks balanced salt solution; IOP: intraocular pressure; LAMP1/2: lysosomal associated membrane protein 1/2; LepB: leptomycin B; MTOR: mechanistic target of rapamacyin kinase; NES: nuclear export signals; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NLS: nuclear localization signal; NPCs: nuclear pore complexes; NUFIP1: nuclear FMR1 interacting protein 1; NS: non-stretched; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; pfu: plaque-forming units; PML: promyelocytic leukemia; RFP: red fluorescent protein; RPS15A: ribosomal protein S15a; RPL26: ribosomal protein L26; rRNA: ribosomal RNA; SIRT1: sirtuin 1; SQSTM1/p62: sequestosome 1; tfLC3: mRFP-GFP tandem fluorescent-tagged LC3; TM: trabecular meshwork; WB: western blot; WDR36: WD repeat domain 36; WGA: wheat germ agglutinin; XPO1/CRM1: exportin 1.

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References

Matsuo T, Uchida H, Matsuo N . Bovine and porcine trabecular cells produce prostaglandin F2 alpha in response to cyclic mechanical stretching. Jpn J Ophthalmol. 1996; 40(3):289-96. View

Kimura S, Fujita N, Noda T, Yoshimori T . Monitoring autophagy in mammalian cultured cells through the dynamics of LC3. Methods Enzymol. 2009; 452:1-12. DOI: 10.1016/S0076-6879(08)03601-X. View

Kuma A, Matsui M, Mizushima N . LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization. Autophagy. 2007; 3(4):323-8. DOI: 10.4161/auto.4012. View

Monemi S, Spaeth G, DaSilva A, Popinchalk S, Ilitchev E, Liebmann J . Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1. Hum Mol Genet. 2005; 14(6):725-33. DOI: 10.1093/hmg/ddi068. View

Terry L, Shows E, Wente S . Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport. Science. 2007; 318(5855):1412-6. DOI: 10.1126/science.1142204. View

Keller K, Bhattacharya S, Borras T, Brunner T, Chansangpetch S, Clark A . Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. Exp Eye Res. 2018; 171:164-173. PMC: 6042513. DOI: 10.1016/j.exer.2018.03.001. View

Xu Y, Wan W, Shou X, Huang R, You Z, Shou Y . TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters. Autophagy. 2016; 12(7):1118-28. PMC: 4990990. DOI: 10.1080/15548627.2016.1175693. View

Kraft C, Deplazes A, Sohrmann M, Peter M . Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol. 2008; 10(5):602-10. DOI: 10.1038/ncb1723. View

Hauser M, Allingham R, Linkroum K, Wang J, LaRocque-Abramson K, Figueiredo D . Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006; 47(6):2542-6. DOI: 10.1167/iovs.05-1476. View

10.

Luna C, Li G, Qiu J, Challa P, Epstein D, Gonzalez P . Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2009; 50(12):5805-10. PMC: 3140847. DOI: 10.1167/iovs.09-3796. View

11.

Olson M, Dundr M, Szebeni A . The nucleolus: an old factory with unexpected capabilities. Trends Cell Biol. 2000; 10(5):189-96. DOI: 10.1016/s0962-8924(00)01738-4. View

12.

Andersen J, Lyon C, Fox A, Leung A, Lam Y, Steen H . Directed proteomic analysis of the human nucleolus. Curr Biol. 2002; 12(1):1-11. DOI: 10.1016/s0960-9822(01)00650-9. View

13.

Gallenberger M, Meinel D, Kroeber M, Wegner M, Milkereit P, Bosl M . Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro. Hum Mol Genet. 2010; 20(3):422-35. DOI: 10.1093/hmg/ddq478. View

14.

Pederson T . The plurifunctional nucleolus. Nucleic Acids Res. 1998; 26(17):3871-6. PMC: 147800. DOI: 10.1093/nar/26.17.3871. View

15.

Hirt J, Liton P . Autophagy and mechanotransduction in outflow pathway cells. Exp Eye Res. 2016; 158():146-153. PMC: 5199638. DOI: 10.1016/j.exer.2016.06.021. View

16.

Boisvert F, van Koningsbruggen S, Navascues J, Lamond A . The multifunctional nucleolus. Nat Rev Mol Cell Biol. 2007; 8(7):574-85. DOI: 10.1038/nrm2184. View

17.

Boulon S, Westman B, Hutten S, Boisvert F, Lamond A . The nucleolus under stress. Mol Cell. 2010; 40(2):216-27. PMC: 2987465. DOI: 10.1016/j.molcel.2010.09.024. View

18.

Hailey D, Rambold A, Satpute-Krishnan P, Mitra K, Sougrat R, Kim P . Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell. 2010; 141(4):656-67. PMC: 3059894. DOI: 10.1016/j.cell.2010.04.009. View

19.

Hu S, Eberhard L, Chen J, Love J, Butler J, Fredberg J . Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device. Am J Physiol Cell Physiol. 2004; 287(5):C1184-91. DOI: 10.1152/ajpcell.00224.2004. View

20.

Maxwell W, Islam M, Graham D, Gennarelli T . A qualitative and quantitative analysis of the response of the retinal ganglion cell soma after stretch injury to the adult guinea-pig optic nerve. J Neurocytol. 1994; 23(6):379-92. DOI: 10.1007/BF01666527. View