English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background   Saccharomyces cerevisiae  ScGdt1 and mammalian TMEM165 are two members of the UPF0016 membrane protein family that is likely to form a new group of Ca 2+ /H +  antiporter and/or a Mn 2+  transporter in the Golgi apparatus. We have previously shown that  Candida albicans CaGDT1  is a functional ortholog of  ScGDT1  in the response of  S. cerevisiae  to calcium stress. However, how CaGdt1 together with the Golgi calcium pump CaPmr1 regulate calcium homeostasis and cell wall integrity in this fungal pathogen remains unknown.    Methods  Chemical sensitivity was tested by dilution assay. Cell survival was examined by measuring colony-forming units and staining with Annexin V-FITC and propidium iodide. Calcium signaling was examined by expression of downstream target gene  CaUTR2 , while cell wall integrity signaling was revealed by detection of phosphorylated Mkc1 and Cek1. Subcellular localization of CaGdt1 was examined through direct and indirect immunofluorescent approaches. Transcriptomic analysis was carried out with RNA sequencing.    Results  This study shows that  Candida albicans CaGDT1  is also a functional ortholog of  ScGDT1  in the response of  S. cerevisiae  to cell wall stress. CaGdt1 is localized in the Golgi apparatus but at distinct sites from CaPmr1 in  C. albicans . Loss of  CaGDT1  increases the sensitivity of cell lacking  CaPMR1  to cell wall and ER stresses. Deletion of  CaGDT1  and/or  CaPMR1  increases calcium uptake and activates the calcium/calcineurin signaling. Transcriptomic profiling reveals that core functions shared by CaGdt1 and CaPmr1 are involved in the regulation of cellular transport of metal ions and amino acids. However, CaGdt1 has distinct functions from CaPmr1. Chitin synthase gene  CHS2  is up regulated in all three mutants, while  CHS3  is only up regulated in the  pmr1/pmr1  and the  gdt1/gdt1 pmr1/pmr1  mutants. Five genes ( DIE2 ,  STT3 ,  OST3 ,  PMT1  and  PMT4 ) of glycosylation pathway and one gene ( SWI4 ) of the cell wall integrity (CWI) pathway are upregulated due to deletion of  CaGDT1  and/or  CaPMR1 . Consistently, deletion of either  CaPMR1  or  CaGDT1  activates the CaCek1-mediated CWI signaling in a cell wall stress-independent fashion. Calcineurin function is required for the integrity of the cell wall and vacuolar compartments of cells lacking both  GDT1  and  CaPMR1 .    Conclusions  CaPmr1 is the major player in the regulation of calcium homeostasis and cell wall stress, while CaGdt1 plays a compensatory role for CaPmr1 in the Golgi compartment in  C. albicans .    Electronic supplementary material  The online version of this article (10.1186/s12964-018-0246-x) contains supplementary material, which is available to authorized users.

cell communication and signaling

CaGdt1 plays a compensatory role for the calcium pump CaPmr1 in the regulation of calcium signaling and cell wall integrity signaling in Candida albicans