The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

Cohen, Yifat, Megyeri, Márton, Chen, Oscar C W, Condomitti, Giuseppe, Riezman, Isabelle, Loizides-Mangold, Ursula, Abdul-Sada, Alaa, Rimon, Nitzan, Riezman, Howard, Platt, Frances M, Futerman, Anthony H and Schuldiner, Maya (2013) The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum. PLoS ONE, 8 (12). e85519. ISSN 1932-6203

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Abstract

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QH Natural history > QH0301 Biology
Depositing User: Tom Gittoes
Date Deposited: 10 Mar 2015 12:46
Last Modified: 23 Mar 2017 05:21
URI: http://sro.sussex.ac.uk/id/eprint/53298

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