predicted to possess 6–12 membrane-
spanning domains. The NBAT proteins
share 80–85% sequence identity and
encode a protein of 683 amino acids with a
non-glycosylated molecular mass of 78
kDa.
As noted, the expression of NBAT
mRNA in oocytes results in increased
system bo,+ activity. Paradoxically, how-
ever, the expression of NBAT cDNA in
mammalian cells has failed to result in
increased system bo,+activity.Because of
its unique predicted membrane topo-
graphy, and because rat kidney NBAT
appears to be associated with another pro-
tein of 50 kDa in size via disulphide
bridging, it currently is thought that NBAT
encodes a protein that activates an endo-
genous oocyte transporter, or that serves as
an accessory subunit, rather than encoding
a discrete transport protein.
System y+L activity mediates the Na+-
independent absorption of cationic amino
acids in a manner similar to system bo,+,
except that the transport of zwitterionic
amino acids by system y+L is Na+-depen-
dent and cystine is not a substrate. When
expressed in oocytes, the human T-cell
surface antigen 4F2hc (4F2 heavy chain)
induces both cationic and zwitterionic
amino acid high-affinity uptake in an
system y+L-like manner. Besides similar
substrate recognitions, the 4F2hc and the
NBAT proteins share significant (30%)
sequence similarities and predicted mem-
brane topographies. 4F2hc is an 85 kDa
type II membrane glycoprotein that spans
the membrane a single time and that forms
a heterodimer functional unit with the
45 kDa non-glycosylated 4F2 light chain
protein (Malandro and Kilberg, 1996).
Implicit with its shared homology to 4F2hc,
the system bo,+/NBAT transport system may
be composed of multiple proteins.
Because of their broad substrate
specificity, the expression of NBAT and
4F2hc transport proteins/systems is con-
sidered to be important for rapid cellular
growth. NBAT mRNA and protein are most
highly expressed in the kidney and small
intestine, but many other tissues express
lower levels of NBAT mRNA. In the rat,
NBAT has been localized specifically to
the epithelia of kidney proximal tubule
and jejunal microvilli. Similarly, many
polarized epithelial cells express 4F2hc
mRNA and system y+L activity. Based on
the electroneutrality of transport across the
basolateral membranes and consistent with
its obligate exchanger function, it appears
that system y+L activity is localized to the
basolateral membrane of polarized cells. In
the apical membranes of enterocytes,
systems Bo,+, y+and bo,+ have all been
measured, depending on diet, cell type and
species differences. Accordingly, as a
general model, the transport of cationic
amino acids across polarized cells is pro-
posed to occur by the transport of substrate
across the apical membrane due to varying
contributions by systems Bo,+, bo,+and/or
y+, followed by transfer across the baso-
lateral membrane by system y+L (Deves
and Boyd, 1998). The expression on the
apical membrane of multiple transporters
with differing relative affinities for the
same substrates ensures that the potential
to absorb cationic substrates will be
maximal at whatever concentration they
are present.PepT family of H+/peptide co-transportersPepT1 (peptide transporter 1 ; a 707 amino
acid polypeptide for rabbit and a 708
amino acid polypeptide for human) cDNA
encodes a low-affinity, high-capacity trans-
porter that is predicted to contain one rela-
tively large cytosolic domain and 12
-helical membrane-spanning domains (Fei
et al., 1994). PepT2 cDNA encodes a high-
affinity, low-capacity transporter that is
predicted to consist of 729 amino acids and
possess 12 membrane-spanning domains
(Leibach and Ganapathy, 1996). The amino
acid sequences for human PepT1 and
PepT2 share 50% identity, with the
majority of the homology existing in the
membrane-spanning regions.
The number of H+ions required for
the intestinal apical membrane peptide
transport system depends on the charge of
the substrate; PepT1 displays H+:substrate14 J.C. Matthews