M. Yokode et al., CYTOPLASMIC SEQUENCE REQUIRED FOR BASOLATERAL TARGETING OF LDL RECEPTOR IN LIVERS OF TRANSGENIC MICE, The Journal of cell biology, 117(1), 1992, pp. 39-46
When expressed in livers of transgenic mice, the human low density lip
oprotein (LDL) receptor is specifically targeted to the basolateral (s
inusoidal) surface of hepatocytes as determined by immunofluorescence
and immunoelectron microscopy. The COOH-terminal cytoplasmic domain of
the receptor (residues 790-839) contains a signal for this targeting.
A mutant receptor truncated at residue 812 was localized exclusively
to the apical (bile canalicular) surface. A mutant receptor terminatin
g at residue 829 showed the normal basolateral distribution, as did a
receptor in which alanine was substituted for serine 833, which was pr
eviously shown to be a site for phosphorylation in vitro. These data l
ocalize the basolateral targeting signal to the 17-residue segment bet
ween residues 812 and 828. A 10-amino acid stretch within this segment
shows a 4/10 match with a sequence within a previously identified bas
olateral sorting motif for the receptor for polymeric IgA/IgM in MDCK
cells. The four shared residues are spaced at intervals of three, rais
ing the possibility that they all face the same side of an alpha-helix
. We conclude that this 10-amino acid stretch may contain a signal tha
t directs certain proteins, including the LDL receptor and the polymer
ic IgG/IgM receptor, to the basolateral surface of polarized epithelia
.