The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast.

• Arsenic is widely distributed in nature and all organisms possess regulatory mechanisms to evade toxicity and acquire tolerance. Yet, little is known about arsenic sensing and signaling mechanisms or about their impact on tolerance and detoxification systems. Here, we describe a novel role of the S. cerevisiae mitogen-activated protein kinase Hog1p in protecting cells during exposure to arsenite and the related metalloid antimonite. Cells impaired in Hog1p function are metalloid hypersensitive, whereas cells with elevated Hog1p activity display improved tolerance. Hog1p is phosphorylated in response to arsenite and this phosphorylation requires Ssk1p and Pbs2p. Arsenite-activated Hog1p remains primarily cytoplasmic and does not mediate a major transcriptional response. Instead, hog1delta sensitivity is accompanied by elevated cellular arsenic levels and we demonstrate that increased arsenite influx is dependent on the aquaglyceroporin Fps1p. Fps1p is phosphorylated on threonine 231 in vivo and this phosphorylation critically affects Fps1p activity. Moreover, Hog1p is shown to affect Fps1p phosphorylation. Our data are the first to demonstrate Hog1p activation by metalloids and provides a mechanism by which this kinase contributes to tolerance acquisition. Understanding how arsenite/antimonite uptake and toxicity is modulated may prove of value for their use in medical therapy.

Ämnesord

NATURVETENSKAP  -- Kemi -- Fysikalisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Physical Chemistry (hsv//eng)

Nyckelord

Arsenites

pharmacokinetics

toxicity

Cytoplasm

metabolism

Gene Expression Regulation

Fungal

Membrane Proteins

drug effects

metabolism

physiology

Membrane Transport Proteins

physiology

Mitogen-Activated Protein Kinases

genetics

physiology

Models

Biological

Mutation

Phosphorylation

Protein Transport

drug effects

Saccharomyces cerevisiae

drug effects

Saccharomyces cerevisiae Proteins

drug effects

genetics

metabolism

physiology

Signal Transduction

Teratogens

pharmacokinetics

toxicity

Threonine

Transcription

Genetic

Teratogens

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)