Membrane movements of E-cadherin

Paterson, Andrew Dylan. (2004). Membrane movements of E-cadherin PhD Thesis, School of Biomedical Sciences, The University of Queensland.

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Author Paterson, Andrew Dylan.
Thesis Title Membrane movements of E-cadherin
School, Centre or Institute School of Biomedical Sciences
Institution The University of Queensland
Publication date 2004
Thesis type PhD Thesis
Supervisor Prof Alpha Yap
Total pages 214
Collection year 2004
Language eng
Subjects 270100 Biochemistry and Cell Biology
Formatted abstract

E-cadherin is a single pass transmembrane adhesion receptor. Its cytoplasmic tail associates with proteins collectively termed catenins while the ectodomains engage in homophilic adhesion in a calcium-dependent manner. The cadherin complex is associated with the actin cytoskeleton and is involved in the modulation of actin filaments. E-cadherin predominantly localises to adherens junctions (AJ) and through the establishment of AJ is involved in the generation of polarised epithelia. Conversely, loss of E-cadherin drives cells into a mesenchymal phenotype, an important step in the progression of metastic tumours. E-cadherin also has been shown to have key roles in tissue morphogenesis and development. The aim of this study is to look into mechanisms that control the trafficking of E-cadherin after it reaches the plasma membrane from the biosynthetic pathway. This study examines the endocytotic pathway of E-cadherin, the signals needed for endocytosis to occur and potential cytoskeletal determinants of cadherin trafficking. 


E-cadherin recycling from the plasma membrane has only recently been discovered, so little is known about the pathway. The results in this study show that E-cadherin enters the endosomal system via a putative macropinocytotic pathway controlled by ARF-6. Once internalised, cadherin molecules are trafficked in the early endosomal system through the same route as transferrin, a well-characterised endocytotic protein. However, the initial internalisation step appeared to occur in a clathrin-independent fashion. By screening a number of cytoplasmic tail mutants lacking known internalisation sequences I found that these regions were not needed for endocytosis of E-cadherin to occur. This further suggested that a non-clathrin macropinocytotic pathway was utilised by E-cadherin in these experiments. 


Lastly, the effect of the microtubules on E-cadherin function was investigated. It has previously been shown that microtubules aid in cadherin trafficking, but the effects of the microtubule-E-cadherin interaction is largely unknown. By using fluorescence recovery after photobleaching (FRAP) techniques, I was able to show that microtubules aid in the turnover of E-cadherin in these junctions. Immunofluorescence and live cell imaging experiments demonstrated that microtubules could be transiently captured and tethered at cadherin based adhesive contacts. This capture process may involve the plus-end binding protein CLIP-170 and the cadherin associated protein IQGAP. I propose a model where IQGAP can capture microtubules via CLIP-170 and tether them to the E-cadherin complex. This provides a novel potential link between cadherins and microtubules. 

Keyword Cell receptors

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
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Created: Tue, 07 Feb 2012, 11:11:50 EST by Bekti Mulatiningsih on behalf of The University of Queensland Library