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Download StatisticsArab, Maryam (2020). The role of CD82 in desmosomal adhesion. University of Birmingham. Ph.D.
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Arab2020PhD.pdf
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Abstract
Desmosomes are intercellular junctions that provide tissues with mechanical strength. They are abundant in epithelial tissues and the myocardium. PKCα plays an important role in the assembly of desmosomes and in the regulation of adhesiveness of desmosomes in tissues. Tetraspanins are four-pass transmembrane proteins that are able to interact amongst themselves and with membrane proteins and cytoplasmic signalling proteins to form tetraspanin-enriched microdomains. The tetraspanin CD82 has been shown to strengthen E-cadherin-β-catenin interactions and recruit PKCα to the membrane. The aim of this thesis was to investigate the role of CD82 in desmosomal adhesion.
Overexpression of CD82 in HB2 mammary epithelial cells increases cell-cell adhesion. The CD82 mediated increase in cell-cell adhesion is brought about by an increase in both desmosomal and adherens junction mediated adhesion. Interaction studies revealed that CD82 interacts with PKCα, and PKCα interacts with the C-terminal domain of desmoplakin and phosphorylates it. CD82 does not interact directly with desmoplakin but it could potentially localise PKCα at the membrane, enabling it to phosphorylate desmoplakin, so promoting desmosome assembly and cell adhesion. Direct stochastic optical reconstruction microscopy revealed that CD82 does not affect the clustering of desmosomal proteins but instead alters the organisation of the desmosomal plaque, reducing the distance between desmoplakin C-terminal domains. Overall these findings show that CD82 mediates an increase in desmosomal adhesion by a mechanism that could involve PKCα-mediated desmoplakin phosphorylation and reorganisation of desmoplakin within the desmosomal plaque.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (former) > College of Medical & Dental Sciences | |||||||||
| School or Department: | Institute of Cancer and Genomic Sciences | |||||||||
| Funders: | Biotechnology and Biological Sciences Research Council | |||||||||
| Subjects: | Q Science > QH Natural history > QH301 Biology | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/10203 |
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