A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics
Keratins exert important structural but also cytoprotective functions. They have to be adaptable to support cellular homeostasis. Epiplakin (EPPK1) has been shown to decorate keratin filaments in epithelial cells and to play a protective role under stress, but the mechanism is still unclear. Using l...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/19/3077 |
| _version_ | 1797479929117409280 |
|---|---|
| author | Sonia Ratajczyk Corinne Drexler Reinhard Windoffer Rudolf E. Leube Peter Fuchs |
| author_facet | Sonia Ratajczyk Corinne Drexler Reinhard Windoffer Rudolf E. Leube Peter Fuchs |
| author_sort | Sonia Ratajczyk |
| collection | DOAJ |
| description | Keratins exert important structural but also cytoprotective functions. They have to be adaptable to support cellular homeostasis. Epiplakin (EPPK1) has been shown to decorate keratin filaments in epithelial cells and to play a protective role under stress, but the mechanism is still unclear. Using live-cell imaging of epithelial cells expressing fluorescently tagged EPPK1 and keratin, we report here an unexpected dynamic behavior of EPPK1 upon stress. EPPK1 was diffusely distributed throughout the cytoplasm and not associated with keratin filaments in living cells under standard culture conditions. However, ER-, oxidative and UV-stress, as well as cell fixation, induced a rapid association of EPPK1 with keratin filaments. This re-localization of EPPK1 was reversible and dependent on the elevation of cytoplasmic Ca<sup>2+</sup> levels. Moreover, keratin filament association of EPPK1 led to significantly reduced keratin dynamics. Thus, we propose that EPPK1 stabilizes the keratin network in stress conditions, which involve increased cytoplasmic Ca<sup>2+</sup>. |
| first_indexed | 2024-03-09T21:53:49Z |
| format | Article |
| id | doaj.art-6e96362ce5584545aa74d0c7c5a6d7b2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:53:49Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6e96362ce5584545aa74d0c7c5a6d7b22023-11-23T20:02:22ZengMDPI AGCells2073-44092022-09-011119307710.3390/cells11193077A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin DynamicsSonia Ratajczyk0Corinne Drexler1Reinhard Windoffer2Rudolf E. Leube3Peter Fuchs4Max Perutz Labs, Department of Biochemistry and Cell Biology, University of Vienna, Vienna Biocenter Campus (VBC), A-1030 Vienna, AustriaMax Perutz Labs, Department of Biochemistry and Cell Biology, University of Vienna, Vienna Biocenter Campus (VBC), A-1030 Vienna, AustriaInstitute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, GermanyInstitute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, GermanyMax Perutz Labs, Department of Biochemistry and Cell Biology, University of Vienna, Vienna Biocenter Campus (VBC), A-1030 Vienna, AustriaKeratins exert important structural but also cytoprotective functions. They have to be adaptable to support cellular homeostasis. Epiplakin (EPPK1) has been shown to decorate keratin filaments in epithelial cells and to play a protective role under stress, but the mechanism is still unclear. Using live-cell imaging of epithelial cells expressing fluorescently tagged EPPK1 and keratin, we report here an unexpected dynamic behavior of EPPK1 upon stress. EPPK1 was diffusely distributed throughout the cytoplasm and not associated with keratin filaments in living cells under standard culture conditions. However, ER-, oxidative and UV-stress, as well as cell fixation, induced a rapid association of EPPK1 with keratin filaments. This re-localization of EPPK1 was reversible and dependent on the elevation of cytoplasmic Ca<sup>2+</sup> levels. Moreover, keratin filament association of EPPK1 led to significantly reduced keratin dynamics. Thus, we propose that EPPK1 stabilizes the keratin network in stress conditions, which involve increased cytoplasmic Ca<sup>2+</sup>.https://www.mdpi.com/2073-4409/11/19/3077cytoskeletonkeratinintermediate filamentsplakin protein familyepiplakin |
| spellingShingle | Sonia Ratajczyk Corinne Drexler Reinhard Windoffer Rudolf E. Leube Peter Fuchs A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics Cells cytoskeleton keratin intermediate filaments plakin protein family epiplakin |
| title | A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics |
| title_full | A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics |
| title_fullStr | A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics |
| title_full_unstemmed | A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics |
| title_short | A Ca<sup>2+</sup>-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics |
| title_sort | ca sup 2 sup mediated switch of epiplakin from a diffuse to keratin bound state affects keratin dynamics |
| topic | cytoskeleton keratin intermediate filaments plakin protein family epiplakin |
| url | https://www.mdpi.com/2073-4409/11/19/3077 |
| work_keys_str_mv | AT soniaratajczyk acasup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT corinnedrexler acasup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT reinhardwindoffer acasup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT rudolfeleube acasup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT peterfuchs acasup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT soniaratajczyk casup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT corinnedrexler casup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT reinhardwindoffer casup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT rudolfeleube casup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics AT peterfuchs casup2supmediatedswitchofepiplakinfromadiffusetokeratinboundstateaffectskeratindynamics |