Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting.

Abstract:

:Conditional cdc1(Ts) mutants of S. cerevisiae arrest with a phenotype similar to that exhibited by Mn(2+)-depleted cells. Sequence similarity between Cdc1p and a class of Mn(2+)-dependent phosphoesterases, as well as the observation that conditional cdc1(Ts) growth can be ameliorated by Mn(2+) supplement, suggests that Cdc1p activity is sensitive to intracellular Mn(2+) levels. This article identifies several previously uncharacterized cdc1(Ts) suppressors as class E vps (vacuolar protein sorting) mutants and shows that these, as well as other vps mutants, accumulate high levels of intracellular Mn(2+). Yeast VPS genes play a role in delivery of membrane transporters to the vacuole for degradation, and we show that the vps mutants accumulate elevated levels of the high-affinity Mn(2+) transporter Smf1p. cdc1(Ts) conditional growth is also alleviated by mutations, including doa4 and ubc4, that compromise protein ubiquitination, and these ubiquitination defects are associated with Smf1p accumulation. Epistasis studies show that these suppressors require functional Smf1p to alleviate the cdc1(Ts) growth defect, whereas Smf1p is dispensable for cdc1(Ts) suppression by a mutation (cos16/per1) that does not influence intracellular Mn(2+) levels. Because Smf1p is ubiquitinated in vivo, we propose that Smf1p is targeted to the vacuole for degradation by ubiquitination-dependent protein sorting.

journal_name

Genetics

journal_title

Genetics

authors

Eguez L,Chung YS,Kuchibhatla A,Paidhungat M,Garrett S

doi

10.1534/genetics.167.1.107

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

107-17

issue

1

eissn

0016-6731

issn

1943-2631

pii

167/1/107

journal_volume

167

pub_type

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