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Doctoral thesis
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The Role of WW-PLEKHAs and PDZD11 in the Trafficking of the Copper Pump ATP7A and in Copper Homeostasis

ContributorsSluysmans, Sophie
DirectorsCiti, Sandraorcid
Imprimatur date2021-08-04
Defense date2021-07-23
Abstract

PLEKHA5 and PLEKHA6 are newly identified proteins from the PLEKHA family which harbor a N-terminal tandem of WW domains that bind to PDZD11, similarly to the junctional protein PLEKHA7. PLEKHA5 and PLEKHA6 have a tissue distribution and subcellular localization distinct from PLEKHA7, since they are present at lateral cell-cell contacts, and additionally along microtubules in the case of PLEKHA5 and at junctions concerning PLEKHA6. Key structural domains, i. e. WW, PH and coiled-coil motifs, direct the distinct subcellular distributions of WW-PLEKHAs (PLEKHA5, PLEKHA6 and PLEKHA7), defining different subcellular pools of PDZD11. By promoting the binding of PDZD11 with the C-terminal PDZ-binding domain of the Menkes copper pump ATP7A, WW-PLEKHAs together with PDZD11 mediate the copper-induced distribution of ATP7A from the trans-Goli network to the cell periphery in polarized kidney epithelial cells, and are required to limit the increase of intracellular copper levels when cells are exposed to elevated copper conditions.

eng
Keywords
  • PLEKHA5
  • PLEKHA6
  • PLEKHA7
  • Menkes copper pump ATP7A
  • PDZD11
  • Copper homeostasis
  • WW-PLEKHAs
Citation (ISO format)
SLUYSMANS, Sophie. The Role of WW-PLEKHAs and PDZD11 in the Trafficking of the Copper Pump ATP7A and in Copper Homeostasis. 2021. doi: 10.13097/archive-ouverte/unige:155198
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Creation10/01/2021 8:18:00 AM
First validation10/01/2021 8:18:00 AM
Update time03/19/2024 4:52:05 PM
Status update03/19/2024 4:52:05 PM
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