Desmosomes As Signaling Hubs in the Regulation of Cell Behavior

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Oct 11

PMID 34631720

Citations 31

Authors

Lisa Muller

Mechthild Hatzfeld

Rene Keil

Affiliations

Soon will be listed here.

Abstract

Desmosomes are intercellular junctions, which preserve tissue integrity during homeostatic and stress conditions. These functions rely on their unique structural properties, which enable them to respond to context-dependent signals and transmit them to change cell behavior. Desmosome composition and size vary depending on tissue specific expression and differentiation state. Their constituent proteins are highly regulated by posttranslational modifications that control their function in the desmosome itself and in addition regulate a multitude of desmosome-independent functions. This review will summarize our current knowledge how signaling pathways that control epithelial shape, polarity and function regulate desmosomes and how desmosomal proteins transduce these signals to modulate cell behavior.

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References

Rogers S, Harrington K, Rhys-Evans P, O-Charoenrat P, Eccles S . Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev. 2005; 24(1):47-69. DOI: 10.1007/s10555-005-5047-1. View

Hakuno F, Takahashi S . IGF1 receptor signaling pathways. J Mol Endocrinol. 2018; 61(1):T69-T86. DOI: 10.1530/JME-17-0311. View

Bass-Zubek A, Hobbs R, Amargo E, Garcia N, Hsieh S, Chen X . Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly. J Cell Biol. 2008; 181(4):605-13. PMC: 2386101. DOI: 10.1083/jcb.200712133. View

Nestor-Bergmann A, Stooke-Vaughan G, Goddard G, Starborg T, Jensen O, Woolner S . Decoupling the Roles of Cell Shape and Mechanical Stress in Orienting and Cueing Epithelial Mitosis. Cell Rep. 2019; 26(8):2088-2100.e4. PMC: 6381790. DOI: 10.1016/j.celrep.2019.01.102. View

Arribas J, Borroto A . Protein ectodomain shedding. Chem Rev. 2002; 102(12):4627-38. DOI: 10.1021/cr010202t. View

Kamekura R, Nava P, Feng M, Quiros M, Nishio H, Weber D . Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier. Mol Biol Cell. 2015; 26(18):3165-77. PMC: 4569309. DOI: 10.1091/mbc.E15-03-0147. View

Hatzfeld M, Haffner C, Schulze K, Vinzens U . The function of plakophilin 1 in desmosome assembly and actin filament organization. J Cell Biol. 2000; 149(1):209-22. PMC: 2175088. DOI: 10.1083/jcb.149.1.209. View

Ferone G, Mollo M, Thomason H, Antonini D, Zhou H, Ambrosio R . p63 control of desmosome gene expression and adhesion is compromised in AEC syndrome. Hum Mol Genet. 2012; 22(3):531-43. PMC: 3542863. DOI: 10.1093/hmg/dds464. View

Bendrick J, Eldredge L, Williams E, Haight N, Dubash A . Desmoplakin Harnesses Rho GTPase and p38 Mitogen-Activated Protein Kinase Signaling to Coordinate Cellular Migration. J Invest Dermatol. 2018; 139(6):1227-1236. PMC: 6535125. DOI: 10.1016/j.jid.2018.11.032. View

10.

Mohammed F, Chidgey M . Desmosomal protein structure and function and the impact of disease-causing mutations. J Struct Biol. 2021; 213(3):107749. DOI: 10.1016/j.jsb.2021.107749. View

11.

Chen Y, Chang J, Lee L, Wang H, Liao C, Chiu C . DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. Oncogene. 2006; 26(3):467-76. DOI: 10.1038/sj.onc.1209802. View

12.

Chen S, Gurha P, Lombardi R, Ruggiero A, Willerson J, Marian A . The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy. Circ Res. 2013; 114(3):454-68. PMC: 3946717. DOI: 10.1161/CIRCRESAHA.114.302810. View

13.

Cai F, Zhu Q, Miao Y, Shen S, Su X, Shi Y . Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2. J Cancer Res Clin Oncol. 2016; 143(1):59-69. DOI: 10.1007/s00432-016-2250-0. View

14.

Lacouture M . Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006; 6(10):803-12. DOI: 10.1038/nrc1970. View

15.

Wallis S, Lloyd S, Wise I, Ireland G, Fleming T, Garrod D . The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells. Mol Biol Cell. 2000; 11(3):1077-92. PMC: 14832. DOI: 10.1091/mbc.11.3.1077. View

16.

Pasparakis M, Haase I, Nestle F . Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol. 2014; 14(5):289-301. DOI: 10.1038/nri3646. View

17.

Kalyankrishna S, Grandis J . Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006; 24(17):2666-72. DOI: 10.1200/JCO.2005.04.8306. View

18.

Rietscher K, Wolf A, Hause G, Rother A, Keil R, Magin T . Growth Retardation, Loss of Desmosomal Adhesion, and Impaired Tight Junction Function Identify a Unique Role of Plakophilin 1 In Vivo. J Invest Dermatol. 2016; 136(7):1471-1478. DOI: 10.1016/j.jid.2016.03.021. View

19.

Bosveld F, Bellaiche Y . Tricellular junctions. Curr Biol. 2020; 30(6):R249-R251. DOI: 10.1016/j.cub.2020.01.029. View

20.

Eckhart L, Lachner J, Tschachler E, Rice R . TINCR is not a non-coding RNA but encodes a protein component of cornified epidermal keratinocytes. Exp Dermatol. 2020; 29(4):376-379. PMC: 7187231. DOI: 10.1111/exd.14083. View