Abstract
ABSTRACTCalcium signaling can elicit different pathways involved in an extreme variety of biological processes. Calcium levels must be tightly regulated in a spatial and temporal manner in order to be efficiently and properly utilized in the host physiology. The Ca2+-ATPase, encoded by pmr-1 gene, was first identified in yeast and localized to the Golgi and it appears to be involved in calcium homeostasis. PMR-1 function is evolutionary conserved from yeast to human, where mutations in the orthologous gene ATP2C1 cause Hailey-Hailey disease. In this work, we used the Caenorhabditis elegans model system to gain insight into the downstream response elicited by the loss of pmr-1 gene. We found that pmr-1 knocked down animals not only showed defects in the oligosaccharide structure of glycoproteins at the cell surface but also were characterized by reduced susceptibility to bacterial infection. Although increased resistance to the infection might be related to lack of regular recognition of C. elegans surface glycoproteins by microbial agents, we provide genetic evidence that pmr-1 interfered nematodes mounted a stronger innate immune response to Gram-positive bacterial infection. Thus, our observations indicate pmr-1 as a candidate gene implicated in mediating the worm’s innate immune response.
Highlights
Pmr-1 gene encodes a P-type ATPase that regulates Ca2+ and Mn2+ homeostasis
In order to evaluate the effect of the inactivation of the Ca2+-ATPase PMR-1 in C. elegans on glycosylation process, the pmr-1 gene was silenced by feeding RNAi
The levels of pmr-1 transcript of individuals subjected to RNA interference, normalized for the housekeeping gene act-1, were considerably lower than the transcript derived from nematodes treated with the empty vector (Fig. S1)
Summary
PMR-1 is located in the Golgi apparatus and it is involved in glycosylation, protein sorting and ER-associated protein degradation in the secretory pathway as demonstrated by studies on the homologous protein of Saccharomyces cerevisiae and Kluyveromyces lactis yeasts [1,2,3,4]. A normal concentration of the Ca2+ ion inside the Golgi apparatus and the Endoplasmic Reticulum seems to be necessary for the functional activity of the enzymes involved in N- and O-glycosylation, as well as for a regular secretion of glycoproteins and a normal degradation associated with the ER of misfolded proteins [5]. HHD is an autosomal dominant skin disorder in which despite the association of mutation of ATP2C1 with the disease, its in vivo role remains poorly investigated [7,8,9]. The yeast model has provided important information that can explain how in Hailey-
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call