Coupling of melanocyte signaling and mechanics by caveolae is required for human skin pigmentation.
Caveolae
/ metabolism
Caveolin 1
/ metabolism
Cell Communication
/ physiology
Cells, Cultured
Coculture Techniques
Epidermal Cells
/ metabolism
Epidermis
/ metabolism
HeLa Cells
Humans
Keratinocytes
/ cytology
Melanocytes
/ cytology
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Signal Transduction
/ physiology
Skin
/ cytology
Skin Pigmentation
/ physiology
Ultraviolet Rays
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 06 2020
12 06 2020
Historique:
received:
24
06
2019
accepted:
15
05
2020
entrez:
14
6
2020
pubmed:
14
6
2020
medline:
25
8
2020
Statut:
epublish
Résumé
Tissue homeostasis requires regulation of cell-cell communication, which relies on signaling molecules and cell contacts. In skin epidermis, keratinocytes secrete factors transduced by melanocytes into signaling cues promoting their pigmentation and dendrite outgrowth, while melanocytes transfer melanin pigments to keratinocytes to convey skin photoprotection. How epidermal cells integrate these functions remains poorly characterized. Here, we show that caveolae are asymmetrically distributed in melanocytes and particularly abundant at the melanocyte-keratinocyte interface in epidermis. Caveolae in melanocytes are modulated by ultraviolet radiations and keratinocytes-released factors, like miRNAs. Preventing caveolae formation in melanocytes increases melanin pigment synthesis through upregulation of cAMP signaling and decreases cell protrusions, cell-cell contacts, pigment transfer and epidermis pigmentation. Altogether, we identify that caveolae serve as molecular hubs that couple signaling outputs from keratinocytes to mechanical plasticity of pigment cells. The coordination of intercellular communication and contacts by caveolae is thus crucial to skin pigmentation and tissue homeostasis.
Identifiants
pubmed: 32532976
doi: 10.1038/s41467-020-16738-z
pii: 10.1038/s41467-020-16738-z
pmc: PMC7293304
doi:
Substances chimiques
Caveolin 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2988Références
Hoath, S. B. & Leahy, D. G. The organization of human epidermis: functional epidermal units and phi proportionality. J. Invest. Dermatol. 121, 1440–1446 (2003).
pubmed: 14675195
doi: 10.1046/j.1523-1747.2003.12606.x
Christiansen, J. H., Coles, E. G. & Wilkinson, D. G. Molecular control of neural crest formation, migration and differentiation. Curr. Opin. Cell Biol. 12, 719–724 (2000).
pubmed: 11063938
doi: 10.1016/S0955-0674(00)00158-7
Delevoye, C., Marks, M. S. & Raposo, G. Lysosome-related organelles as functional adaptations of the endolysosomal system. Curr. Opin. Cell Biol. 59, 147–158 (2019).
pubmed: 31234051
doi: 10.1016/j.ceb.2019.05.003
Raposo, G., Tenza, D., Murphy, D. M., Berson, J. F. & Marks, M. S. Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells. J. Cell Biol. 152, 809–823 (2001).
pubmed: 11266471
pmcid: 2195785
doi: 10.1083/jcb.152.4.809
Wu, X. & Hammer, J. A. Melanosome transfer: It is best to give and receive. Curr. Opin. Cell Biol. 29, 1–7 (2014).
pubmed: 24662021
doi: 10.1016/j.ceb.2014.02.003
Abdel-Malek, Z. et al. Analysis of the UV-induced melanogenesis and growth arrest of human melanocytes. Pigment Cell Res. 7, 326–332 (1994).
pubmed: 7533905
doi: 10.1111/j.1600-0749.1994.tb00635.x
Hirobe, T. Keratinocytes regulate the function of melanocytes. Dermatol. Sin. 32, 200–204 (2014).
doi: 10.1016/j.dsi.2014.05.002
Lo Cicero, A. et al. Exosomes released by keratinocytes modulate melanocyte pigmentation. Nat. Commun. 6, 7506 (2015).
pubmed: 26103923
doi: 10.1038/ncomms8506
D’Mello, S. A. N., Finlay, G. J., Baguley, B. C. & Askarian-Amiri, M. E. Signaling pathways in melanogenesis. Int. J. Mol. Sci. 17, 1144 (2016).
pmcid: 4964517
doi: 10.3390/ijms17071144
Saldana-Caboverde, A. & Kos, L. Roles of endothelin signaling in melanocyte development and melanoma. Pigment Cell Melanoma Res. 23, 160–170 (2011).
doi: 10.1111/j.1755-148X.2010.00678.x
Buscà, R. & Ballotti, R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 13, 60–69 (2000).
pubmed: 10841026
doi: 10.1034/j.1600-0749.2000.130203.x
Scott, G. Rac and Rho: the story behind melanocyte dendrite formation. Pigment Cell Res. 15, 322–330 (2002).
pubmed: 12213087
doi: 10.1034/j.1600-0749.2002.02056.x
Scott, G. & Leopardi, S. The cAMP signaling pathway has opposing effects on Rac and Rho in B16F10 cells: Implications for dendrite formation in melanocytic cells. Pigment Cell Res. 16, 139–148 (2003).
pubmed: 12622791
doi: 10.1034/j.1600-0749.2003.00022.x
Palade, G. E. Fine structure of blood capillaries. J. Appl. Phys. 24, 1424 (1953).
Yamada, E. The fine structures of the gall bladder epithelium of the mouse. J. Biophys. Biochem. Cytol. 1, 445–458 (1955).
pubmed: 13263332
pmcid: 2229656
doi: 10.1083/jcb.1.5.445
Stan, R. V. Structure of caveolae. Biochim. Biophys. Acta 1746, 334–348 (2005).
pubmed: 16214243
doi: 10.1016/j.bbamcr.2005.08.008
Williams, T. M. & Lisanti, M. P. The caveolin proteins. Genome Biol. 5, 214 (2004).
Nassar, Z. D. & Parat, M. O. Cavin family: new players in the biology of caveolae. Int. Rev. Cell Mol. Biol. 320, 235–305 (2015).
pubmed: 26614875
doi: 10.1016/bs.ircmb.2015.07.009
Cheng, J. P. X. & Nichols, B. J. Caveolae: one function or many? Trends Cell Biol. 26, 177–189 (2016).
pubmed: 26653791
doi: 10.1016/j.tcb.2015.10.010
Lamaze, C., Tardif, N., Dewulf, M., Vassilopoulos, S. & Blouin, C. M. The caveolae dress code: structure and signaling. Curr. Opin. Cell Biol. 47, 117–125 (2017).
pubmed: 28641181
doi: 10.1016/j.ceb.2017.02.014
Harvey, R. D. & Calaghan, S. C. Caveolae create local signalling domains through their distinct protein content, lipid profile and morphology. J. Mol. Cell Cardiol. 52, 366–375 (2012).
pubmed: 21782827
doi: 10.1016/j.yjmcc.2011.07.007
Toya, Y., Schwencke, C., Couet, J., Lisanti, M. P. & Ishikawa, Y. Inhibition of adenylyl cyclase by caveolin peptides. Endocrinology 139, 2025–2031 (1998).
pubmed: 9528990
doi: 10.1210/endo.139.4.5957
Wright, P. T. et al. Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling. J. Mol. Cell Cardiol. 67, 38–48 (2014).
pubmed: 24345421
doi: 10.1016/j.yjmcc.2013.12.003
Wright, P. T. et al. Cardiomyocyte membrane structure and cAMP compartmentation produce anatomical variation in β2AR-cAMP responsiveness in murine hearts. Cell Rep. 23, 459–469 (2018).
pubmed: 29642004
pmcid: 5912947
doi: 10.1016/j.celrep.2018.03.053
Sinha, B. et al. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144, 402–413 (2011).
pubmed: 21295700
pmcid: 3042189
doi: 10.1016/j.cell.2010.12.031
Lo, H. P. et al. The caveolin-Cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. J. Cell Biol. 210, 833–849 (2015).
pubmed: 26323694
pmcid: 4555827
doi: 10.1083/jcb.201501046
Lim, Y.-W. et al. Caveolae protect notochord cells against catastrophic mechanical failure during development. Curr. Biol. 27, 1968–1981.e7 (2017).
pubmed: 28648821
doi: 10.1016/j.cub.2017.05.067
Cheng, J. P. X. et al. Caveolae protect endothelial cells from membrane rupture during increased cardiac output. J. Cell Biol. 211, 53–61 (2015).
pubmed: 26459598
pmcid: 4602045
doi: 10.1083/jcb.201504042
Dewulf, M. et al. Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells. Nat. Commun. 10, 1974 (2019).
pubmed: 31036801
pmcid: 6488599
doi: 10.1038/s41467-019-09405-5
Benito-Martínez, S. et al. Research techniques made simple: cell biology methods for the analysis of pigmentation. J. Investig. Dermatol. 140, 257–268.e8 (2020).
pubmed: 31980058
doi: 10.1016/j.jid.2019.12.002
Rappel, W. J. & Edelstein-Keshet, L. Mechanisms of cell polarization. Curr. Opin. Syst. Biol. 3, 43–53 (2017).
pubmed: 29038793
pmcid: 5640326
doi: 10.1016/j.coisb.2017.03.005
Wedlich-Soldner, R. & Li, R. Spontaneous cell polarization: undermining determinism. Nat. Cell Biol. 5, 267–270 (2003).
pubmed: 12669070
doi: 10.1038/ncb0403-267
Mayor, S., Parton, R. G. & Donaldson, J. G. Clathrin-independent pathways of endocytosis. Cold Spring Harb. Perspect. Biol. 6, a016758 (2014).
pubmed: 24890511
pmcid: 4031960
doi: 10.1101/cshperspect.a016758
Studer, D., Humbel, B. M. & Chiquet, M. Electron microscopy of high pressure frozen samples: bridging the gap between cellular ultrastructure and atomic resolution. Histochem. Cell Biol. 130, 877–889 (2008).
pubmed: 18795316
doi: 10.1007/s00418-008-0500-1
Richter, T. et al. High-resolution 3D quantitative analysis of caveolar ultrastructure and caveola-cytoskeleton interactions. Traffic 9, 893–909 (2008).
pubmed: 18397183
doi: 10.1111/j.1600-0854.2008.00733.x
Ali, N. et al. Skin equivalents: skin from reconstructions as models to study skin development and diseases. Br. J. Dermatol. 173, 391–403 (2015).
pubmed: 25939812
doi: 10.1111/bjd.13886
Heuser, J. Three-dimensional visualization of coated vesicle formation in fibroblasts. J. Cell Biol. 84, 560–583 (1980).
pubmed: 6987244
doi: 10.1083/jcb.84.3.560
Allen, J. A. et al. Caveolin-1 and lipid microdomains regulate Gs trafficking and attenuate Gs/adenylyl cyclase signaling. Mol. Pharmacol. 76, 1082–1093 (2009).
pubmed: 19696145
pmcid: 2774991
doi: 10.1124/mol.109.060160
Litvin, T. N., Kamenetsky, M., Zarifyan, A., Buck, J. & Levin, L. R. Kinetic properties of ‘soluble’ adenylyl cyclase: synergism between calcium and bicarbonate. J. Biol. Chem. 278, 15922–15926 (2003).
pubmed: 12609998
doi: 10.1074/jbc.M212475200
Lu, J., Zhang, J., Wang, Y. & Sun, Q. Caveolin-1 scaffolding domain peptides alleviate liver fibrosis by inhibiting TGF-β1/Smad signaling in mice. Int. J. Mol. Sci. 19, E1729 (2018).
Weng, P. et al. Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme oxygenase-1 through interrupting its interact with caveolin-1. Oncotarget 8, 40104–40114 (2017).
pubmed: 28402952
pmcid: 5522314
doi: 10.18632/oncotarget.16676
Imokawa, G., Yada, Y. & Kimura, M. Signalling mechanisms of endothelin-induced mitogenesis and melanogenesis in human melanocytes. Biochem. J. 314, 305–312 (1996).
pubmed: 8660299
pmcid: 1217041
doi: 10.1042/bj3140305
Abdel-Malek, Z. et al. Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. Proc. Natl Acad. Sci. USA 92, 1789–1793 (1995).
pubmed: 7878059
doi: 10.1073/pnas.92.5.1789
Ebanks, J. P., Wickett, R. R. & Boissy, R. E. Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration. Int. J. Mol. Sci. 10, 4066–4087 (2009).
pubmed: 19865532
pmcid: 2769151
doi: 10.3390/ijms10094066
Theos, A. C., Truschel, S. T., Raposo, G. & Marks, M. S. The silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment Cell Res. 18, 322–336 (2005).
pubmed: 16162173
pmcid: 2788625
doi: 10.1111/j.1600-0749.2005.00269.x
Neves-Zaph, S. R. Phosphodiesterase diversity and signal processing within cAMP signaling networks. Adv. Neurobiol. 17, 3–14 (2017).
pubmed: 28956327
doi: 10.1007/978-3-319-58811-7_1
Wojtal, K. A., Hoekstra, D. & Van Ijzendoorn, S. C. D. cAMP-dependent protein kinase A and the dynamics of epithelial cell surface domains: Moving membranes to keep in shape. BioEssays 30, 146–155 (2008).
pubmed: 18200529
doi: 10.1002/bies.20705
Howe, A. K. Regulation of actin-based cell migration by cAMP/PKA. Biochim. Biophys. Acta 1692, 159–174 (2004).
pubmed: 15246685
doi: 10.1016/j.bbamcr.2004.03.005
Kippenberger, S., Bernd, A., Bereiter-Hahn, J., Ramirez-Bosca, A. & Kaufmann, R. The mechanism of melanocyte dendrite formation: the impact of differentiating keratinocytes. Pigment Cell Res. 11, 34–37 (1998).
pubmed: 9523333
doi: 10.1111/j.1600-0749.1998.tb00708.x
Grande-García, A. et al. Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. J. Cell Biol. 177, 683–694 (2007).
pubmed: 17517963
pmcid: 2064213
doi: 10.1083/jcb.200701006
Chugh, P. & Paluch, E. K. The actin cortex at a glance. J. Cell Sci. 131, jcs186254 (2018).
Heissler, S. M. & Manstein, D. J. Nonmuscle myosin-2: mix and match. Cell Mol. Life Sci. 70, 1–21 (2013).
pubmed: 22565821
doi: 10.1007/s00018-012-1002-9
Diz-Muñoz, A., Fletcher, D. A. & Weiner, O. D. Use the force: membrane tension as an organizer of cell shape and motility. Trends Cell Biol. 23, 47–53 (2013).
pubmed: 23122885
doi: 10.1016/j.tcb.2012.09.006
Tadokoro, R. & Takahashi, Y. Intercellular transfer of organelles during body pigmentation. Curr. Opin. Genet. Dev. 45, 132–138 (2017).
pubmed: 28605672
doi: 10.1016/j.gde.2017.05.001
Conde-Perez, A. et al. A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity. Nat. Commun. 6, 8093 (2015).
pubmed: 26307673
pmcid: 4560817
doi: 10.1038/ncomms9093
Ostrom, R. S. et al. Localization of adenylyl cyclase isoforms and G protein-coupled receptors in vascular smooth muscle cells: expression in caveolin-rich and noncaveolin domains. Mol. Pharmacol. 62, 983–992 (2002).
pubmed: 12391260
doi: 10.1124/mol.62.5.983
Gu, C., Smith, K. E., Hu, B., Cooper, D. M. F. & Fagan, K. A. Residence of adenylyl cyclase type 8 in caveolae is necessary but not sufficient for regulation by capacitative Ca 2+ entry. J. Biol. Chem. 277, 6025–6031 (2002).
pubmed: 11744699
doi: 10.1074/jbc.M109615200
Collins, B. M., Davis, M. J., Hancock, J. F. & Parton, R. G. Structure-based reassessment of the caveolin signaling model: do caveolae regulate signaling through caveolin-protein interactions? Dev. Cell 23, 11–20 (2012).
pubmed: 22814599
pmcid: 3427029
doi: 10.1016/j.devcel.2012.06.012
Goetz, J. G. et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 146, 148–163 (2011).
pubmed: 21729786
pmcid: 3244213
doi: 10.1016/j.cell.2011.05.040
Averaimo, S. et al. A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors. Nat. Commun. 7, 12896 (2016).
pubmed: 27694812
pmcid: 5059439
doi: 10.1038/ncomms12896
Head, B. P. et al. Neuron-targeted caveolin-1 protein enhances signaling and promotes arborization of primary neurons. J. Biol. Chem. 286, 33310–33321 (2011).
pubmed: 21799010
pmcid: 3190943
doi: 10.1074/jbc.M111.255976
Navarro, A., Anand-Apte, B. & Parat, M.-O. A role for caveolae in cell migration. FASEB J. 18, 1801–1811 (2004).
pubmed: 15576483
doi: 10.1096/fj.04-2516rev
Gallagher, S. J. et al. Beta-catenin inhibits melanocyte migration but induces melanoma metastasis. Oncogene 32, 2230–2238 (2013).
pubmed: 22665063
doi: 10.1038/onc.2012.229
Valencia, J. C. Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes. J. Cell Sci. 119, 1080–1091 (2006).
pubmed: 16492709
pmcid: 4629779
doi: 10.1242/jcs.02804
Newton, R. A., Cook, A. L., Roberts, D. W., Leonard, J. H. & Sturm, R. A. Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes. J. Invest. Dermatol. 127, 2216–2227 (2007).
pubmed: 17460731
doi: 10.1038/sj.jid.5700840
Gauthier, N. C., Fardin, M. A., Roca-Cusachs, P. & Sheetz, M. P. Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading. Proc. Natl Acad. Sci. USA 108, 14467–14472 (2011).
pubmed: 21808040
doi: 10.1073/pnas.1105845108
Carè, A., Parolini, I., Felicetti, F. & Sargiacomo, M. in Caveolins in Cancer Pathogenesis, Prevention and Therapy (eds Mercier, I., Jasmin, J.-F. & Lisantia, M. P.) 65–74 (Springer US, 2011).
Kruglikov, I. L. & Scherer, P. E. Caveolin-1 as a pathophysiological factor and target in psoriasis. npj Aging Mech. Dis. 5, 4 (2019).
Lobos-González, L., Aguilar, L., Fernández, G., Sanhueza, C. & Quest, A. F. G. in Advances in Malignant Melanoma - Clinical and Research Perspectives (ed Armstrong, A.) (InTech, 2019).
Lin, M. I., Yu, J., Murata, T. & Sessa, W. C. Caveolin-1—deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. Cancer Res. 67, 2849–2856 (2007).
pubmed: 17363608
doi: 10.1158/0008-5472.CAN-06-4082
MacKie, R. M. Long-term health risk to the skin of ultraviolet radiation. Prog. Biophys. Mol. Biol. 92, 92–96 (2006).
pubmed: 16616325
doi: 10.1016/j.pbiomolbio.2006.02.008
Huang, R.-Y. et al. An exploration of the role of microRNAs in psoriasis: a systematic review of the literature. Medicine 94, e2030 (2015).
pubmed: 26559308
pmcid: 4912302
doi: 10.1097/MD.0000000000002030
Salducci, M. et al. Factors secreted by irradiated aged fibroblasts induce solar lentigo in pigmented reconstructed epidermis. Pigment Cell Melanoma Res. 27, 502–504 (2014).
pubmed: 24533682
doi: 10.1111/pcmr.12234
Ripoll, L. et al. Myosin VI and branched actin filaments mediate membrane constriction and fission of melanosomal tubule carriers. J. Cell Biol. 217, 2709–2726 (2018).
pubmed: 29875258
pmcid: 6080934
doi: 10.1083/jcb.201709055
Hurbain, I. et al. Electron tomography of early melanosomes: implications for melanogenesis and the generation of fibrillar amyloid sheets. Proc. Natl Acad. Sci. USA 105, 19726–19731 (2008).
pubmed: 19033461
doi: 10.1073/pnas.0803488105
Hurbain, I., Romao, M., Bergam, P., Heiligenstein, X. & Raposo, G. Analyzing lysosome-related organelles by electron microscopy. Methods Mol. Biol. 1594, 43–71 (2017).
pubmed: 28456976
doi: 10.1007/978-1-4939-6934-0_4
Mastronarde, D. N. Dual-axis tomography: an approach with alignment methods that preserve resolution. J. Struct. Biol. 120, 343–352 (1997).
pubmed: 9441937
doi: 10.1006/jsbi.1997.3919
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996).
pubmed: 8742726
doi: 10.1006/jsbi.1996.0013
Sommer, C., Straehle, C., Kothe, U. & Hamprecht, F. A. Ilastik: Interactive learning and segmentation toolkit. In Proc. International Symposium on Biomedical Imaging 230–233. https://doi.org/10.1109/ISBI.2011.5872394 (2011).