Maintenance of epidermal architecture by CLASP2 and p120-catenin

• Autores: Marta Násila Shahbazi Alonso
• Directores de la Tesis: Mirna Pérez Moreno (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2013
• Idioma: inglés
• Tribunal Calificador de la Tesis: Amparo Cano (presid.), Xavier Trepat (secret.), Fernando Martín Belmonte (voc.), Marcos Malumbres (voc.), Carien Niessen (voc.)
• Materias:
  • Química
    • Bioquímica
      • Biología molecular
  • Ciencias de la vida
    • Biología animal (zoología)
      • Histología animal
    • Biología celular
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • Adherens Junctions are cadherin-based structures fundamental for the maintenance of cell-cell adhesion, and thus preservation of proper tissue architecture and function. To do so, they establish connections with the cytoskeleton, both with actin filaments and microtubules, enabling cells to respond to injury and external stimuli as a coordinated tissue.

    Previous findings have illustrated connections between cadherins and microtubule minus- and plus-ends. However, the functional relevance of such interactions and the molecular players are still under debate. Moreover, the involvement of these particular connections in the homeostasis of specific tissues remains unexplored.

    In this thesis project we investigated how microtubules reach Adherens Junctions in basal cells of the epidermis. We identified a novel interaction between the microtubule plus-end binding protein CLASP2 and the cadherin binding molecule p120 at Adherens Junctions. In the absence of CLASP2, Adherens Junctions do not form properly and present altered dynamics, which leads to a disruption of cell-cell adhesion. This phenotype is accompanied by alterations in microtubule dynamics at Adherens Junctions, in terms of speed and directionality. The same alterations are observed in the absence of p120, suggesting that the CLASP2-p120 interaction contributes to microtubule targeting to Adherens Junctions.

    Importantly, since CLASP2 expression is enriched in basal progenitor cells of the epidermis, the CLASP2-p120 interaction seems to be restricted to this specific epidermal compartment, where it may dynamically regulate cell-cell adhesion. On the contrary, the microtubule minus-end binding protein Nezha localizes to cell-cell contacts in suprabasal differentiated keratinocytes. Loss of CLASP2 leads to alterations in the proliferation-differentiation balance of basal keratinocytes. This alteration could be the result of weakened Adherens Junctions but it may also reflect a defect in the correct orientation of the spindle via interaction with p120.

    Overall, the work presented in this doctoral thesis supports a model where microtubule plus-ends are targeted to Adherens Junctions in basal keratinocytes via the CLASP2-p120 interaction whereas minus-ends are captured at cell-cell adhesion sites in differentiated cells. This could be an important mechanism to control Adherens Junction stability and dynamics in epidermal progenitor cells.