Schöler, Jonas. Molecular mechanisms of teneurin function in transcriptional regulation and cell adhesion. 2015, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11222
The first part of my thesis discusses the evolution of teneurins. Teneurins are ancient proteins that are well-conserved across phyla from unicellular eukaryotic organisms like the choanoflagellate Monosiga brevicollis to higher multicellular organisms like vertebrates. The study suggests that teneurins may have evolved from a choanoflagellate via horizontal gene transfer from a prokaryote. It also describes the structural features of teneurins in detail, and identifies splice variants of chicken and human teneurin ICDs.
The second part of my thesis describes a novel molecular mechanism in transcriptional regulation for the intracellular domain of human teneurin-1 (TEN1-ICD). We identified several new interaction partners of the TEN1-ICD in a yeast-2 hybrid screen. Concurrently, we performed a whole transcriptome analysis of a glioblastoma cell line engineered for inducible overexpressing of the TEN1-ICD comparing induced to non-induced cells, to determine potential target genes. Results included several microphthalmia-associated transcription factor (MITF) target genes. Interestingly, MITF is directly inhibited at the promoter by transcriptional repressor histidine-triad nucleotide binding protein 1 (HINT1), one of the novel TEN1-ICD interaction partners. Further experiments show that the TEN1-ICD competes for HINT1 binding to positively regulate MITF-dependent transcription of target gene GPNMB.
The third part of my thesis discusses the NHL repeat domain, located in the ECD of teneurins. Since this predicted beta-propeller is responsible for homophilic, but not heterophilic interactions in chicken teneurins-1 and -2, we were interested to learn more about the structure of the domain. For this, we started by purifying the NHL repeat domain of chicken teneurin-2 and set up drops for crystallization studies, to resolve the structure by X-ray crystallography. We have set up the purification protocol, but have not yet determined the ‘right’ conditions for crystallization of the protein.
|Committee Members:||Tucker, Richard P.|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI > Cell communication in growth control and differentiation (Chiquet-Ehrismann)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||153 S.|
|Last Modified:||30 Jun 2016 10:57|
|Deposited On:||18 May 2015 15:00|
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