TITLE:
Inhibition of MAPK Hog1 Results in Increased Hsp104 Aggregate Formation Probably through Elevated Arsenite Influx into the Cells, an Approach with Numerous Potential Applications
AUTHORS:
Doryaneh Ahmadpour, Amin A. Banaeiyan, Morten Grøtli, Martin Adiels, Mattias Goksör, Caroline B. Adiels
KEYWORDS:
Mitogen Activated Protein Kinase (MAPK); Hog1; MAPK inhibitor; Arsenic; Microfluidics
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.4 No.2,
April
1,
2014
ABSTRACT:
Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in
the environment, contaminating water and soil and accumulating in crops.
Paradoxically, arsenic is also part of modern therapy and employed in treating
numerous ailments and diseases. Hence, inventing strategies to tune cellular arsenic
uptake based on purpose is striking. Here, we describe an approach in which the
arsenite uptake can be increased using a MAPK inhibitor. Employing microfluidic
flow chambers in combination with optical tweezers and fluorescent microscopy,
we elevated the influx of arsenite into the yeast Saccharomyces cerevisiae cells following short-term treatment with
a Hog1 kinase inhibitor. The increase in arsenite uptake was followed on
arsenite triggered redistribution of a reporter protein, Hsp104-GFP, which was imaged
over time. The effect was even more pronounced when the yeast mother and
daughter cells were analyzed disjointedly, an opportunity provided owing to
single-cell analysis. Our data firstly provide a strategy to increase arsenite
uptake and secondly show that arsenite triggered aggregates, previously shown
to be sites of damaged proteins, are distributed asymmetrically and less accumulated
in daughter cells. Inventing approaches to tune arsenite uptake has a great
value for its use in environmental as well as medical applications.