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Caveolin-1 in Müller Glia Exists as Heat-Resistant, High Molecular Weight Complexes

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Retinal Degenerative Diseases XIX

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1415))

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Abstract

Caveolin-1 (Cav1), the core structural and scaffolding protein of caveolae membrane domains, is highly expressed in many retinal cells and is associated with ocular diseases. Cav1 regulates innate immune responses and is implicated in neuroinflammatory and neuroprotective signaling in the retina. We have shown that Cav1 expression in Müller glia accounts for over 70% of all retinal Cav1 expression. However, the proteins interacting with Cav1 in Müller glia are not established. Here, we show that immortalized MIO-M1 Müller glia, like endogenous Müller glia, highly express Cav1. Surprisingly, we found that Cav1 in MIO-M1 cells exists as heat-resistant, high molecular weight complexes that are stable after immunoprecipitation (IP). Mass spectrometric analysis of high molecular weight Cav1 complexes after Cav1 IP revealed an interactome network of intermediate filament, desmosomes, and actin-, and microtubule-based cytoskeleton. These results suggest Cav1 domains in Müller glia act as a scaffolding nexus for the cytoskeleton.

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References

  1. Aung CS, Hill MM, Bastiani M, Parton RG, Parat MO. PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9. Eur J Cell Biol. 2011;90:136–42.

    Article  CAS  PubMed  Google Scholar 

  2. Chow BW, Gu C. Gradual suppression of transcytosis governs functional blood-retinal barrier formation. Neuron. 2017;93:1325–1333 e1323.

    Article  Google Scholar 

  3. Cohen AW, Hnasko R, Schubert W, Lisanti MP. Role of caveolae and caveolins in health and disease. Physiol Rev. 2004;84:1341–79.

    Article  CAS  PubMed  Google Scholar 

  4. Fletcher DA, Mullins RD. Cell mechanics and the cytoskeleton. Nature. 2010;463:485–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Glenney JR Jr. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem. 1989;264:20163–6.

    Article  CAS  PubMed  Google Scholar 

  6. Glenney JR Jr, Soppet D. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc Natl Acad Sci U S A. 1992;89:10517–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gu X, Fliesler SJ, Zhao YY, Stallcup WB, Cohen AW, Elliott MH. Loss of caveolin-1 causes blood-retinal barrier breakdown, venous enlargement, and mural cell alteration. Am J Pathol. 2014a;184:541–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gu X, Reagan A, Yen A, Bhatti F, Cohen AW, Elliott MH. Spatial and temporal localization of caveolin-1 protein in the developing retina. Adv Exp Med Biol. 2014b;801:15–21.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gu X, Reagan AM, McClellan ME, Elliott MH. Caveolins and caveolae in ocular physiology and pathophysiology. Prog Retin Eye Res. 2017;56:84–106.

    Article  CAS  PubMed  Google Scholar 

  10. Gurley JM, Elliott MH. The role of caveolin-1 in retinal inflammation. Adv Exp Med Biol. 2019;1185:169–73.

    Article  CAS  PubMed  Google Scholar 

  11. Gurley JM, Gmyrek GB, McClellan ME, Hargis EA, Hauck SM, Dozmorov MG, Wren JD, Carr DJJ, Elliott MH. Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina. Invest Ophthalmol Vis Sci. 2020;61:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hauck SM, Dietter J, Kramer RL, Hofmaier F, Zipplies JK, Amann B, Feuchtinger A, Deeg CA, Ueffing M. Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry. Mol Cell Proteom. 2010;9:2292–305.

    Article  CAS  Google Scholar 

  13. Hayer A, Stoeber M, Bissig C, Helenius A. Biogenesis of caveolae: stepwise assembly of large caveolin and cavin complexes. Traffic. 2010;11:361–82.

    Article  CAS  PubMed  Google Scholar 

  14. Hill MM, Bastiani M, Luetterforst R, Kirkham M, Kirkham A, Nixon SJ, Walser P, Abankwa D, Oorschot VM, Martin S, Hancock JF, Parton RG. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell. 2008;132:113–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Inder KL, Zheng YZ, Davis MJ, Moon H, Loo D, Nguyen H, Clements JA, Parton RG, Foster LJ, Hill MM. Expression of PTRF in PC-3 Cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Mol Cell Proteom. 2012;11:M111012245.

    Article  Google Scholar 

  16. Khater IM, Aroca-Ouellette ST, Meng F, Nabi IR, Hamarneh G. Caveolae and scaffold detection from single molecule localization microscopy data using deep learning. PLoS One. 2019a;14:e0211659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Khater IM, Liu Q, Chou KC, Hamarneh G, Nabi IR. Super-resolution modularity analysis shows polyhedral caveolin-1 oligomers combine to form scaffolds and caveolae. Sci Rep. 2019b;9:9888.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Klaassen I, Hughes JM, Vogels IM, Schalkwijk CG, Van Noorden CJ, Schlingemann RO. Altered expression of genes related to blood-retina barrier disruption in streptozotocin-induced diabetes. Exp Eye Res. 2009;89:4–15.

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Gu X, Boyce TM, Zheng M, Reagan AM, Qi H, Mandal N, Cohen AW, Callegan MC, Carr DJ, Elliott MH. Caveolin-1 increases proinflammatory chemoattractants and blood-retinal barrier breakdown but decreases leukocyte recruitment in inflammation. Invest Ophthalmol Vis Sci. 2014;55:6224–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu L, Brown D, McKee M, Lebrasseur NK, Yang D, Albrecht KH, Ravid K, Pilch PF. Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance. Cell Metab. 2008;8:310–7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell. 2015;161:1202–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mirza MK, Yuan J, Gao XP, Garrean S, Brovkovych V, Malik AB, Tiruppathi C, Zhao YY. Caveolin-1 deficiency dampens Toll-like receptor 4 signaling through eNOS activation. Am J Pathol. 2010;176:2344–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nelson BR, Ueki Y, Reardon S, Karl MO, Georgi S, Hartman BH, Lamba DA, Reh TA. Genome-wide analysis of Muller glial differentiation reveals a requirement for Notch signaling in postmitotic cells to maintain the glial fate. PLoS One. 2011;6:e22817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Parton RG. Caveolae: structure, function, and relationship to disease. Annu Rev Cell Dev Biol. 2018;34:111–36.

    Article  CAS  PubMed  Google Scholar 

  25. Parton RG, del Pozo MA. Caveolae as plasma membrane sensors, protectors and organizers. Nat Rev Mol Cell Biol. 2013;14:98–112.

    Article  CAS  PubMed  Google Scholar 

  26. Roesch K, Jadhav AP, Trimarchi JM, Stadler MB, Roska B, Sun BB, Cepko CL. The transcriptome of retinal Muller glial cells. J Comp Neurol. 2008;509:225–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG. Caveolin, a protein component of caveolae membrane coats. Cell. 1992;68:673–82.

    Article  CAS  PubMed  Google Scholar 

  28. Sargiacomo M, Scherer PE, Tang Z, Kubler E, Song KS, Sanders MC, Lisanti MP. Oligomeric structure of caveolin: implications for caveolae membrane organization. Proc Natl Acad Sci U S A. 1995;92:9407–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Stitt AW, Burke GA, Chen F, McMullen CB, Vlassara H. Advanced glycation end-product receptor interactions on microvascular cells occur within caveolin-rich membrane domains. FASEB J. 2000;14:2390–2.

    Article  CAS  PubMed  Google Scholar 

  30. Thorleifsson G, Walters GB, Hewitt AW, Masson G, Helgason A, DeWan A, Sigurdsson A, Jonasdottir A, Gudjonsson SA, Magnusson KP, Stefansson H, Lam DS, Tam PO, Gudmundsdottir GJ, Southgate L, Burdon KP, Gottfredsdottir MS, Aldred MA, Mitchell P, St Clair D, Collier DA, Tang N, Sveinsson O, Macgregor S, Martin NG, Cree AJ, Gibson J, Macleod A, Jacob A, Ennis S, Young TL, Chan JC, Karwatowski WS, Hammond CJ, Thordarson K, Zhang M, Wadelius C, Lotery AJ, Trembath RC, Pang CP, Hoh J, Craig JE, Kong A, Mackey DA, Jonasson F, Thorsteinsdottir U, Stefansson K. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet. 2010;42:906–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang XM, Kim HP, Nakahira K, Ryter SW, Choi AM. The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1. J Immunol. 2009;182:3809–18.

    Article  CAS  PubMed  Google Scholar 

  32. Wang XM, Kim HP, Song R, Choi AM. Caveolin-1 confers antiinflammatory effects in murine macrophages via the MKK3/p38 MAPK pathway. Am J Respir Cell Mol Biol. 2006;34:434–42.

    Article  CAS  PubMed  Google Scholar 

  33. Wang Z, Liu CH, Huang S, Fu Z, Tomita Y, Britton WR, Cho SS, Chen CT, Sun Y, Ma JX, He X, Chen J. Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier. Sci Adv. 2020;6:eaba7457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wisniewski JR. Filter-aided sample preparation for proteome analysis. Methods Mol Biol. 2018;1841:3–10.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by NIH Grants R01EY019494 (MHE) and NEI Core Grant P30EY021725, by Presbyterian Health Foundation Research Scholar Award to Eric Enyong, and by an unrestricted grant to the OUHSC Department of Ophthalmology from Research to Prevent Blindness, Inc. Virginie Sjoelund was supported in part by the National Institute of General Medical Sciences of the National Institutes of Health under award number P20GM103447. We thank the Laboratory for Molecular Biology and Cytometry Research at OUHSC for the use of the Core Facility, which provided the proteomics services.

Author information

Authors and Affiliations

  1. Department of Physiology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Eric N. Enyong, Jami Gurley & Michael H. Elliott

  2. Department of Ophthalmology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Eric N. Enyong, Jami Gurley & Michael H. Elliott

  3. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Virginie Sjoelung

Authors
  1. Eric N. Enyong
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  2. Jami Gurley
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  3. Virginie Sjoelung
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  4. Michael H. Elliott
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Corresponding author

Correspondence to Michael H. Elliott .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    John D. Ash

  2. Ocular Genomics InstituteDepartment of OphthalmologyMassachusetts Eye and Ear InfirmaryHarvard Medical School, Boston, MA, USA

    Eric Pierce

  3. Health Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Robert E. Anderson

  4. Department of Ophthalmology, Duke Medical Center, Durham, NC, USA

    Catherine Bowes Rickman

  5. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Joe G. Hollyfield

  6. Laboratory for Retinal Cell BiologyDepartment of OphthalmologyUniversity Hospital Zurich, University of Zurich, Schlieren, Switzerland

    Christian Grimm

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© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

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Enyong, E.N., Gurley, J., Sjoelung, V., Elliott, M.H. (2023). Caveolin-1 in Müller Glia Exists as Heat-Resistant, High Molecular Weight Complexes. In: Ash, J.D., Pierce, E., Anderson, R.E., Bowes Rickman, C., Hollyfield, J.G., Grimm, C. (eds) Retinal Degenerative Diseases XIX. Advances in Experimental Medicine and Biology, vol 1415. Springer, Cham. https://doi.org/10.1007/978-3-031-27681-1_36

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