A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria.

Abstract

A novel Saccharomyces cerevisiae mutant, unable to grow in the presence of 12.5 mM EGTA, was isolated by replica plating. The phenotype of the mutant is caused by a single amino acid change (Gly'49 to Arg) leu2, his3, ade2, trpl, ura3), leu2, his3, ade2, trpl, ura3), E20 (MA Ta, masi), and CRB1-5A (MATa, leu2, his3, his4-4Q1, trpl, ura3-52, HOLJ-1, masl-ts) were used. EGTA-sensitive mutants were generated by exposing yeast cells to ethyl methanesulfonate (EMS) as described (14) and replica plating on YPD plates (pH 6.0) containing 50 mM Mes and 12.5 mM EGTA. The mutants denoted as csp (chelator-sensitive phenotype) were back-crossed to the wild-type strain as described elsewhere (15)

Manganese transport in eukaryotes: The role of DMT1

“…when cells have a sufficient amount of Mn 2+ ions, Smf1p appears to contribute little to cellular Mn levels. This was corroborated in mutants that lack SMF1 where Mn accumulation was indistinguishable from wild type controls (Supek et al, 1996). Yeasts containing a deletion of the SMF2 gene lose the ability to acquire normal levels of the metal (Luk et al, 2001;Pinner et al, 1997).…”

“…In animals, the transporter can be located both at the cell surface and in intracellular organelles (Nelson, 1999), whereas in S. cerevisiae, the different isoforms are situated at distinct cellular sites: Smf1p at the cell surface, Smf2p in the intracellular vesicles and Smf3p at the vacuolar membrane (Portnoy et al, 2002;Portnoy et al, 2000;Supek et al, 1996).…”

“…Genetic screens first identified the Smf1p transporting Mn across the plasma membrane of yeast cells (Supek et al, 1996). Subsequently, Smf1p was found to be a non-specific metal ion transporter capable of delivering a broader spectrum of essential metal ions such as Mn 2+ , Zn 2+ , Cu 2+ , Fe 2+ and Cd 2+ (Eide, 1998;Nelson, 1999;Supek et al, 1996). Later, it was shown that the yeast genome encodes two additional orthologous proteins, Smf2p and Smf3p, which might also be involved in metal ion transport, but display distinct substrate specificity from Smf1p, implying partially distinct functions for the yeast Smf proteins.…”

“…This sequence conservation implies a functional similarity between human DMT1 and yeast Smfps. Genetic screens first identified the Smf1p transporting Mn across the plasma membrane of yeast cells (Supek et al, 1996). Subsequently, Smf1p was found to be a non-specific metal ion transporter capable of delivering a broader spectrum of essential metal ions such as Mn 2+ , Zn 2+ , Cu 2+ , Fe 2+ and Cd 2+ (Eide, 1998;Nelson, 1999;Supek et al, 1996).…”

Identification of genetic loci controlling bacterial clearance in experimental Salmonella enteritidis infection: an unexpected role of Nramp1 (Slc11a1) in the persistence of infection in mice

“…9,14,17 Nramp1 is part of an ancient family of proteins with highly conserved members in mammals, birds, invertebrates, plants, fungi and even bacteria. [18][19][20][21][22][23][24][25][26] Nramp1 is an integral membrane phosphoglycoprotein located in the late endosome/lysosome compartment of resting macrophages and is recruited to the phagosomal membrane during phagosome maturation 27 that encodes for a divalent-cation transporter. 28 Several additional loci have been found to exert some control during the late phase of infection through their effects on the acquired immune responses.…”