Doctoral thesis
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English

The Role of Paracingulin in the Organization of the Epithelial Microtubule Network

ContributorsFlinois, Arielleorcid
DirectorsCiti, Sandraorcid
Number of pages256
Imprimatur date2023
Defense date2023
Abstract

Cell-cell junctions are a prerequisite of multicellular organisms, allowing the attachment of neighboring cells and their extracellular matrix. Tight and adherens junctions are located at the apical part of the junctional membrane and are crucial for adhesion and the formation of a semipermeable barrier between compartments separated by epithelial and endothelial cell sheets. At the molecular level, both adhesion and barrier functions are mediated by transmembrane proteins and their associated cytoplasmic plaque of proteins. Scaffold and adaptor cytoplasmic proteins act as a signaling hub and link junctions to the cytoskeleton. The shape and mechanical properties of cells are the results of the coordinated functions of the three major cytoskeletal networks: actin filaments, microtubules, and intermediate filaments. The association of actin and actin regulators with junctions has been extensively studied and shows that the actomyosin network is indispensable for adhesion and barrier functions as well as mechanotransduction. However, the extent of the interaction between junctions and microtubules or microtubule-associated proteins and the role of this interaction in epithelial cells is not clear. In this thesis, I sought out to investigate whether the tight and adherens junction protein paracingulin is implicated in the organization of the microtubule network, and through which mechanisms. With a combination of super-resolution microscopy techniques and biochemical experiments, I show that paracingulin interacts with and recruits the microtubule minus-end binding protein CAMSAP3 to junctions, anchoring microtubule minus-ends to cell-cell contacts. Furthermore, knockout of paracingulin in cultured cells and in vivo demonstrates a role for the junctional protein in regulating the organization of the microtubule network in epithelial cells. Together, my thesis work uncovers a new functional association between paracingulin and CAMSAP3 and provides additional evidence for a crosstalk between junctions and the microtubule cytoskeleton.

Keywords
  • Epithelial cell
  • Paracingulin
  • Microtubule
  • Tight junctions
  • Adherens junctions
  • Epithelial microtubule network
Research groups
Citation (ISO format)
FLINOIS, Arielle. The Role of Paracingulin in the Organization of the Epithelial Microtubule Network. Doctoral Thesis, 2023. doi: 10.13097/archive-ouverte/unige:169889
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Creation29/06/2023 15:19:43
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