INVESTIGADORES
VALDEZ Javier Esteban
artículos
Título:
Evolution of differences in transport function in Slc11a family members
Autor/es:
TECHAU ME; VALDEZ TAUBAS J; POPOFF JF; FRANCIS R; SEAMAN M; BLACKWELL JM
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Referencias:
Año: 2007 vol. 282 p. 35646 - 35656
ISSN:
0021-9258
Resumen:
Slc11a1 (formerly Nramp1) is a proton/divalent cation transporter
that regulates cation homeostasis in macrophages.
Slc11a2 mediates divalent cation uptake via the gut and delivery
into cells. The mode of action of the two transporters remains
controversial. Heterologous expression in frog oocytes shows
Slc11a2 is a symporter, whereas Slc11a1 is an antiporter fluxing
divalent cations against the proton gradient. This explains why
Slc11a2, but not Slc11a1, can complement EGTA sensitivity in
smf1 /smf2 /smf3 yeast. However, some studies of transport
in mammalian cells suggest Slc11a1 is a symporter. We now
demonstrate that Slc11a1, but not Slc11a2, complements a divalent
cation stress phenotype in bsd2 /rer1 yeast. This is the
first description of a yeast complementation assay for Slc11a1
function. Given the prior demonstration in frog oocytes that
Slc11a1 acts as an antiporter, the most plausible interpretation
of the data is that Slc11a1 is rescuing bsd2 /rer1 yeast by
exporting divalent cations. Chimaeras define the N terminus,
and a segment of the protein core preceding transmembrane
domain 9 through transmembrane domain 12, as important in
rescuing the divalent cation stress phenotype. EGTA sensitivity
and divalent cation stress phenotypes in yeast expressing Slc11a
orthologues show that symport activity is ancestral. Molecular
changes that mediate rescue of the divalent cation stress phenotype
post-date frogs and co-evolved with Slc11a1 orthologues
that regulate divalent cation homeostasis in macrophages and
resistance to infection in chickens and mammals.