![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, Issue 5, 1801-1807, May 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Biological Sciences, Carnegie Mellon University, Pittsburgh,
Pennsylvania 15213;
Laboratory of Epithelial Cell Biology, Renal-Electrolyte Division, University
of Pittsburgh, Pittsburgh, Pennsylvania 15261
Submitted October 29, 2002;
Revised January 7, 2003;
Accepted January 23, 2003
Monitoring Editor: Vivek Malhotra
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
).
Proteins arriving at the TGN are sorted into either one of these pathways
depending on the type of targeting information they contain, or they traffic
evenly in both pathways if they lack polarized targeting signals. In addition,
a hierarchy of signals exists in polarized sorting, because apical sorting
occurs only in the absence of a functional basolateral signal. Proteins
destined for the apical surface adopt either of two routes to their target
membrane: direct transport from the TGN to the apical membrane or
transcytosis. The direct route to the apical surface is weak or nonexistent in
some polarized cell types, such as hepatocytes
(Bastaki et al.,
2002). In these cells, apically directed proteins are first taken
to the basolateral surface, from which they are internalized and transferred
to the apical plasma membrane.
Unlike apical sorting signals, which may be present in the cytoplasmic,
transmembrane, or lumenal domains of proteins, all the basolateral sorting
signals identified to date lie exclusively in the cytoplasmic domains of the
proteins examined (Aroeti et al.,
1998; Ikonen and Simons,
1998; Nelson and Yeaman,
2001). Basolateral sorting of many membrane proteins, as well as
certain TGN proteins such as TGN38/46 and furin, which cycle to the
basolateral membrane, are dependent on interactions of critical tyrosine- or
leucine-based motifs in the cytoplasmic tail with specific adaptor proteins.
These motifs resemble sequences that specify rapid internalization from the
cell surface, suggesting a relationship between basolateral sorting and
clathrin-mediated endocytosis (Bonifacino
and Dell'Angelica, 1999). Furthermore, an epithelial
cell–specific clathrin adaptor subunit called m1B that interacts
selectively with a subset of tyrosine-based basolateral targeting signals has
been described (Folsch et al.,
1999). These observations and the lack of any counter-examples
have led to the conclusion that basolateral sorting at the TGN occurs solely
by direct interactions of the cytoplasmic sorting signals with coat subunits
mediating basolateral delivery.
Nevertheless, nothing in this data set precludes the possibility that
basolateral sorting may be mediated by "indirect" interactions, in
which a lumenal signal is translated across the membrane by means of a
transmembrane receptor, which in turn interacts with coat proteins at the
cytoplasmic side. In fact, it is arguable that such a mechanism might operate
in basolateral targeting, as similar interactions are used in most other
sorting reactions involving vesicle coat proteins. The most illustrative
example of this is the sorting of soluble cargo. Although it is likely that
many soluble proteins are targeted for secretion at the basolateral surface,
this has not been specifically examined, nor has a receptor for basolateral
cargo been identified. In hepatocytes, "soluble" forms of apical
transmembrane proteins are secreted basolaterally
(Bastaki et al.,
2002). However, basolateral targeting might be considered the
default in this case, because the primary sorting station for these proteins
is the plasma membrane (Nelson and Yeaman,
2001). What is needed, therefore, is identification of a protein
that traffics to the basolateral membrane by use of a lumenal signal and the
cognate receptor acting to translate the signal to coat proteins.
Golgi phosphoprotein of 130 kDa (GPP130) is a somewhat unexpected candidate
for a protein that uses a lumenal basolateral targeting signal. GPP130
exhibits a steady-state localization in the cis-Golgi, mediated by
constant traffic to and retrieval from distal compartments, including the
plasma membrane and endosomes (Puri et
al., 2002). The retrieval mechanism is saturable and requires
acidified lumenal compartments, because either overexpression or elevation of
lumenal pH induces GPP130 redistribution to the cell surface and endosomes.
When acidic pH is restored, GPP130 traffics back to the Golgi
(Linstedt et al.,
1997; Puri et al.,
2002). Importantly, the GPP130 targeting information that mediates
its steady-state localization and reversible redistribution resides solely in
its lumenal domain in a membrane-proximal stretch of 206 amino acids predicted
to form a coiled-coil stem domain (Bachert
et al., 2001). Targeting of GPP130 involves at least
three key sorting steps: local retrieval at the TGN, internalization at the
plasma membrane of molecules that escape this local retrieval, and sorting of
internalized molecules at the sorting endosome into a distinct retrieval
pathway that bypasses the late endosome on its way back to the TGN
(Puri et al., 2002).
This late endosome-bypass pathway has only recently been described in
nonpolarized cells (Mallet and Maxfield,
1999) and has not yet been identified in polarized cells. However,
the best-characterized marker of this pathway, TGN38, is expressed in
polarized cells, and its cycling is known to be basolaterally restricted
(Rajasekaran et al.,
1994). Therefore, GPP130 cycling in polarized cells may be
basolaterally restricted and depend on its lumenal targeting sequences.
To test this hypothesis, we investigated polarized trafficking of GPP130 under conditions of overexpression and elevation of lumenal pH. GPP130 cycling was basolaterally restricted in polarized MDCK cells, and the lumenal stem-targeting domain was both required and sufficient for basolateral trafficking. The role of a lumenal signal strongly suggests a novel receptor-mediated process active in basolateral sorting.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
) and anti-hemagglutinin (12CA5)
(Bachert et al., 2001)
mouse monoclonal antibodies (mAbs) and anti-GPP130
(Puri et al., 2002),
anti-giantin (Puthenveedu and Linstedt,
2001), and anti-transferrin
(Apodaca et al., 1994)
rabbit polyclonal antibodies were used at the dilutions indicated below.
Canine transferrin (Sigma) and transferrin antibodies were kindly provided by
Dr. G. Apodaca (University of Pittsburgh, Pittsburgh, PA). Fluorescently
conjugated goat secondary antibodies were purchased (Zymed, San Francisco,
CA).
Transfection and Cell Culture
Constructs encoding HA-tagged chimeric proteins were generated and cloned
into the mammalian expression vector pCB6 as described previously
(Bachert et al.,
2001). MDCK cells were cultured in minimal essential medium
(Sigma) supplemented with 10% FCS and 100 IU/ml penicillin–streptomycin
at 37°C with 5% CO2. Transfection was by
Ca3(PO4)2 as described previously
(Weisz et al., 1992),
followed by selection using 0.5 mg/ml G418 (Life Technologies Inc., Grand
Island, NY). Transfected cells were isolated by use of cloning rings and
expanded. Nonpolarized-cell immunofluorescence experiments were performed on
cells seeded on 12-mm coverslips. For polarized-cell experiments, cells were
seeded in 12-well transwells (0.4-µm pore; Costar, Cambridge, MA) at 
2
x 105 cells per well. Experiments were performed after 4 d in
culture on filters. Where indicated, the last 14 h of culture before the start
of the experiment were in the presence of 5 mM sodium butyrate. Relative
expression level was determined from immunoblots on whole-cell detergent
lysates as described previously (Linstedt
et al., 1997).
Analysis
Immunofluorescence and image analysis were performed as described
(Linstedt et al.,
1997), except that 0.3% Triton X-100 was used to permeabilize the
cells. Protein localization was performed with anti-GPP130 (diluted 1:200) or
anti-hemagglutinin (diluted 1:200) mAbs. Costaining was with anti-giantin
(diluted 1:500). For antibody uptake experiments, filters were incubated with
antibodies added apically or basolaterally and with transferrin and/or 0.2 mM
chloroquine for 3 h or with 5 µM bafilomycin for 1h, where noted, in MEM
containing 0.6% BSA at 37°C and 5% CO2. Uptake was with either
anti-GPP130 (used at 1:10) or anti-giantin (used at 1:10) mAbs or polyclonal
anti-GPP130 antibody (used at 1:50). Cells were washed with acid wash buffer
(0.2 M glycine, 0.5 M NaCl; pH 2.4) for 10 min on ice before fixation.
Internalized antibodies were detected by staining with anti-mouse or
anti-rabbit secondary antibodies (diluted 1:200). For surface labeling, pairs
of filters were incubated for 20 min with apically or basolaterally added
anti-GPP130 mAbs (used at 1:50) before washing five times with PBS, fixation,
and detection with the conjugated secondary antibodies (1:200). In a modified
version of the surface staining, the filters were incubated with anti-GPP130
(1:50) on both surfaces, washed five times in PBS, incubated for 20 min with
FITC-conjugated secondary antibody (1:50) added basolaterally and
TRITC-conjugated secondary antibody (1:50) added apically, again washed 5
times with PBS, and finally fixed.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
) and chloroquine
(Linstedt et al.,
1997), respectively. Sodium butyrate treatment increased GPP130
expression 2.5- to 3-fold, as determined by immunoblotting (our
unpublished results). Under these conditions, 60% of the cells showed
GPP130 staining in peripheral punctate structures
(Figure 1E) that lacked
staining for giantin (Figure
1F). Cells treated with chloroquine exhibited a striking GPP130
redistribution to punctate structures
(Figure 1G) that lacked giantin
(Figure 1H). Note that
chloroquine treatment altered the giantin pattern but that after treatment,
few GPP130 structures remained coincident with giantin.
|
To ensure that transfected GPP130 cycles to the cell surface and
accumulates in endosomes under conditions of overexpression or lumenal pH
elevation in nonpolarized cells, we allowed uptake of extracellularly applied
anti-GPP130 antibody. In the absence of any treatment, anti-GPP130 mAb uptake
was not detected (Figure 2A). This was expected for properly targeted GPP130, because no uptake was observed
when the same mAb was applied to untreated HeLa cells
(Puri et al., 2002).
Previous work in HeLa cells suggests that this mAb is not sensitive enough to
detect the small amount of GPP130 cycling via the cell surface, whereas this
can be detected using a polyclonal antibody. On induction with sodium
butyrate, GPP130 cycled via the plasma membrane, as indicated by antibody
internalization into punctate peripheral structures
(Figure 2B). Similarly,
treatment with chloroquine yielded robust antibody uptake, indicating cycling
of GPP130 via the surface during its redistribution
(Figure 2C). The internalized
antibodies colocalized extensively with internalized FITC–dextran after
30 min of uptake (Figure 2C,
inset), as previously reported in other cell types
(Linstedt et al.,
1997). As expected, anti-giantin antibodies were not internalized
even when butyrate-induced cells were treated with chloroquine
(Figure 2D). In summary, as
described previously for endogenous GPP130 in other cell lines
(Linstedt et al.,
1997), transfected GPP130 in the stable MDCK cell line exhibited
pH-sensitive and saturable Golgi targeting such that elevation of lumenal pH
or overexpression caused its accumulation in endosomes.
|
Does overexpressed GPP130 cycle via the apical surface, the basolateral
surface, or both? To answer this question, the cells were allowed to polarize
by growth on filters, and then anti-GPP130 antibodies were added to either
side of the filter. In the absence of any additional treatment, anti-GPP130
mAb uptake was not detected from either surface (our unpublished results). In
contrast, after induction of GPP130 expression in polarized MDCK with sodium
butyrate, basolaterally applied anti-GPP130 antibodies yielded a strong
staining of endosomal structures (Figure
3A). Polarity was intact, and GPP130 trafficking was specific to
the basolateral surface, because no uptake of antibody was detected at the
apical surface (Figure 3B).
Transferrin uptake was used as a further positive control for polarity in the
same cells (Fuller and Simons,
1986). As expected, transferrin was internalized preferentially at
the basolateral surface (Figure
3C) but not from the apical surface
(Figure 3D). Nontransfected
MDCK cells did not internalize anti-GPP130 antibodies, and the transfected
MDCK cells did not internalize anti-giantin antibodies (our unpublished
results). GPP130 trafficking to the basolateral surface depended on GPP130
expression level rather than butyrate treatment per se. Transiently
transfected MDCK cells highly overexpressed GPP130 and exhibited antibody
uptake predominantly from the basolateral surface (our unpublished results).
Further, even in the absence of butyrate treatment, the highest GPP130
expressors after stable transfection exhibited basolateral
(Figure 3E) but not apical
(Figure 3F) uptake if the more
sensitive polyclonal anti-GPP130 antibodies were used.
|
Specific cycling via the basolateral domain was also observed when lumenal pH was elevated by use of chloroquine. Anti-GPP130 antibodies were strongly internalized from the basolateral side (Figure 4A) and only minimally from the apical side (Figure 4B). This minimal apical uptake was attributed to a slight disruption of polarity by the chloroquine treatment, as indicated by the internal control. Transferrin uptake was still robust from the basolateral membrane (Figure 4C), but a small amount of uptake was also observed from the apical side (Figure 4D). Bafilomycin, an inhibitor of the proton pump, was also used as a method to raise the lumenal pH. As expected, in bafilomycin-treated cells, anti-GPP130 antibodies were actively internalized when applied at the basolateral surface (Figure 4E), whereas no internalization of apically applied antibodies was observed (Figure 4F). In summary, GPP130 cycling is basolaterally restricted, suggesting the presence of cis-acting sequences that specify polarized targeting.
|
The Luminal Domain of GPP130 Is Both Required and Sufficient for
Basolateral Targeting
To investigate the role of the GPP130 lumenal domain for its basolateral
targeting, we transfected MDCK cells with chimeric constructs containing
versions of the GPP130 lumenal domain fused in frame to the transmembrane and
cytoplasmic domains of DPPIV, an apical plasma membrane protein. The GPP130
lumenal domain is conveniently divided into two segments: the targeting
determinant–containing, coiled-coil stem domain and the larger, highly
acidic C-terminus (Bachert et al.,
2001).
A DPPIV/GPP130 chimera containing the latter segment (GPP130 amino acids
295–696) is plasma membrane localized in nonpolarized cells
(Bachert et al.,
2001). MDCK cells stably expressing this fusion protein were
generated. Under conditions in which the full-length GPP130 was detected only
by basolaterally applied antibodies, the chimeric protein was readily detected
on the surface with anti-GPP130 antibodies applied either basolaterally
(Figure 5A) or apically
(Figure 5B). Because not all
cells expressed detectable amounts of the protein, a separate experiment was
used to confirm that individual cells yielded both basolateral and apical
staining. First, filter-grown cells were exposed to anti-GPP130 antibodies
concurrently at both surfaces. Second, after washing, the basolateral surface
received an FITC-conjugated secondary antibody, and the apical surface
received a TRITC-conjugated secondary antibody. Finally, the cells were imaged
at three focal planes corresponding to the apical, mid, and basal levels.
Single transfected cells showed exclusive TRITC fluorescence at their apical
surface (Figure 5, C and D) and
comparable levels of FITC fluorescence at their basolateral surfaces in the
mid (Figure 5, E and F) and
basal regions (Figure 5, G and
H). All the cells that expressed the protein, irrespective of the
level of expression, showed this nonpolarized distribution.
|
In contrast, a DPPIV/GPP130 chimera containing the lumenal stem domain
(GPP130 amino acids 89–294) behaved similarly to wild-type GPP130. MDCK
cells stably expressing this construct yielded a typical Golgi staining
pattern (Figure 6A) coincident
with costained giantin (Figure
6B). After induction with sodium butyrate, a portion of the
transfected chimera was detectable in peripheral punctate structures that
lacked giantin staining (our unpublished results). Most importantly, when the
cells were allowed to polarize on filter supports and then treated with sodium
butyrate to induce expression, externally applied anti-GPP130 antibodies were
specifically internalized from the basolateral
(Figure 6C), not the apical
(Figure 6D), surface. Note that
because this chimeric protein did not contain the lumenal epitope recognized
by the mAb used above, the uptake experiments presented in
Figure 6 were performed with a
polyclonal antibody developed against the GPP130 stem domain. This antibody
yielded a slight background visible at all surfaces, including those of
noninduced cells (Figure 6, E and
F). In transfected HeLa cells, the lumenal stem domain of GPP130
does not interact in a stable manner with endogenous GPP130
(Bachert et al.,
2001). Furthermore, the same construct is Golgi-localized in HeLa
cells lacking endogenous GPP130 after siRNA-mediated knockdown (manuscript in
preparation). Thus, Golgi localization of the stem domain does not require its
interaction with endogenous GPP130 and it is likely that the same holds true
for its basolateral targeting. In sum, specific antibody uptake from the
basolateral surface of polarized MDCK cells overexpressing a DPPIV/GPP130
chimera containing the lumenal stem domain of GPP130 strongly suggests the
presence of a basolateral sorting signal positioned in the GPP130 lumenal
domain.
|
To test whether the stem domain containing this sorting signal is not only
sufficient but also required for basolateral targeting of GPP130, a construct
lacking this region, 
40–247
(Bachert et al.,
2001), was expressed by transient transfection. In contrast to
wild-type GPP130, which yielded basolateral
(Figure 7A) but not apical
(Figure 7B) antibody uptake,
the stem-deleted version of GPP130 was detected on the surface of all
expressing cells by antibodies applied either basolaterally
(Figure 7C) or apically
(Figure 7D).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
). Although this pathway has not yet been identified in
polarized cells, TGN38 is expressed in polarized cells and is known to be
basolaterally restricted. This suggested that GPP130 also cycles specifically
via the basolateral domain. If so, it seemed likely that such targeting would
depend on lumenal sequences, because GPP130 targeting in nonpolarized cells is
mediated exclusively by lumenal determinants
(Bachert et al.,
2001). Indeed, this was the case. Cycling of GPP130 to the cell
surface, induced by either overexpression or elevation of lumenal pH, was
accompanied by anti-GPP130 uptake only from the basolateral surface.
Importantly, the GPP130 lumenal stem domain was both necessary and sufficient
for the basolaterally restricted surface cycling of GPP130.
On the basis of the lumenal location of the GPP130 basolateral determinant,
GPP130 sorting into the basolateral pathway is most likely mediated by
indirect interactions with cytoplasmic vesicle coat proteins at the TGN. Thus,
it is likely that a basolateral-specific transmembrane "receptor"
mediates packaging of GPP130 into carrier vesicles. This is distinct from, and
possibly competes with, any interactions that mediate retrieval of the protein
from the TGN back to the cis-Golgi. Consistent with such a
basolateral-specific receptor interaction, sorting of GPP130 to the
basolateral surface appeared to be saturable. High-level overexpression of
GPP130, achieved by transient transfection, yielded comparatively weak but
detectable antibody uptake from the apical surface of polarized MDCK cells
(not shown). Further indirect evidence of receptor-mediated targeting comes
from analysis of an early Golgi protein, GP73, that shares many
characteristics with GPP130. GP73 also depends on lumenal stem determinants
for retrieval from the cell surface and endosomes via the late endosome-bypass
pathway (Puri et al.,
2002). Importantly, GPP130 overexpression causes mistargeting of
endogenous GP73, yet they do not seem to interact. Therefore, it is likely
that GP73 trafficking is also basolaterally restricted and that both GP73 and
GPP130 depend on lumenal interactions with the same receptor for their
targeting.
In contrast to the situation for basolateral sorting, apical sorting
frequently involves lumenal determinants, which are primarily sequence
elements that serve as acceptor sites for glycosylation
(Matter, 2000). The mechanism
by which glycans act in apical sorting is not clear, although interactions
with transmembrane lectins might assist enrichment of glycoproteins in
apically targeted vesicles
(Rodriguez-Boulan and Gonzalez,
1999; Matter,
2000). Although GPP130 is glycosylated at either of two adjacent
sites (Linstedt et al.,
1997), these sites are outside the basolateral targeting domain.
Indeed, the DPPIV/GPP130 chimera containing the GPP130 lumenal stem domain
lacked glycosylation sites yet was basolaterally restricted. Also, the GPP130
constructs lacking the stem domain contained the glycosylation sites and
yielded a nonpolarized distribution. Therefore, glycosylation of the GPP130
lumenal domain does not mediate polarized targeting of GPP130.
The extent to which GPP130 cycles to distal basolateral compartments in the
absence of overexpression or elevation of lumenal pH is unknown. However, the
late Golgi lumen is only mildly acidic. This, together with other
considerations (Bachert et al.,
2001), suggests that the pH sensitivity of GPP130 Golgi targeting
is best explained by a model in which GPP130 normally traffics into the late
endosome-bypass pathway, where it encounters a pH-dependent retrieval step.
Inhibition at this step would, over time, cause redistribution of GPP130 and
TGN38 to the same endosomes. Therefore, a significant amount of GPP130 may
move from the TGN to endosomes in untreated cells. The possibility that this
involves, at least in part, cycling via the cell surface is suggested by
surface labeling of GPP130 and anti-GPP130 polyclonal antibody uptake in
untreated HeLa cells (Puri et
al., 2002). It is not known why GPP130 and TGN38 bypass late
endosomes as they move back to the TGN. Perhaps this pathway presents less
chance for spillage into the degradative lysosomal pathway.
Our results suggest the presence of the late endosome-bypass pathway from the basolateral membrane in polarized MDCK cells. Furthermore, because the GPP130 lumenal stem domain mediates both basolateral targeting and endosome-to-Golgi retrieval, a relationship is suggested between the sorting mechanisms active in this pathway and those at the TGN. Therefore, the identification of a lumenal determinant mediating basolateral targeting not only suggests the presence of a basolateral targeting receptor but also provides reagents that could reveal its identity and allow its characterization. This, in turn, may reveal unexpected shared mechanisms in basolateral targeting and endosome-to-Golgi retrieval.
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
|
Footnotes |
|---|
Corresponding author. E-mail address:
linstedt{at}andrew.cmu.edu.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
Aroeti, B., Okhrimenko, H., Reich, V., and Orzech, E. (1998). Polarized trafficking of plasma membrane proteins: emerging roles for coats, SNAREs, GTPases and their link to the cytoskeleton. Biochim. Biophys. Acta 1376%, 57–90.[Medline]
Bachert, C., Lee, T.H., and Linstedt, A.D. (2001).
Lumenal endosomal and Golgi-retrieval determinants involved in pH-sensitive
targeting of an early Golgi protein. Mol. Biol. Cell
12,
3152–3160.
Bastaki, M., Braiterman, L.T., Johns, D.C., Chen, Y.H., and
Hubbard, A.L. (2002). Absence of direct delivery for single
transmembrane apical proteins or their "secretory" forms in
polarized hepatic cells. Mol. Biol. Cell
13,
225–237.
Bonifacino, J.S., and Dell'Angelica, E.C. (1999).
Molecular bases for the recognition of tyrosine-based sorting signals.
J. Cell Biol. 145,
923–926.
Folsch, H., Ohno, H., Bonifacino, J.S., and Mellman, I. (1999). A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell 99, 189–198.[CrossRef][Medline]
Fuller, S.D., and Simons, K. (1986). Transferrin
receptor polarity and recycling accuracy in "tight" and
"leaky" strains of Madin-Darby canine kidney cells. J. Cell
Biol. 103,
1767–1779.
Gorman, C.M., Howard, B.H., and Reeves, R. (1983).
Expression of recombinant plasmids in mammalian cells is enhanced by sodium
butyrate. Nucleic Acids Res.
11,
7631–7648.
Ikonen, E., and Simons, K. (1998). Protein and lipid sorting from the trans-Golgi network to the plasma membrane in polarized cells. Semin. Cell Dev. Biol. 9, 503–509.[CrossRef][Medline]
Linstedt, A.D., Mehta, A., Suhan, J., Reggio, H., and Hauri, H.-P. (1997). Sequence and overexpression of GPP130/GIMPc: evidence for saturable pH-sensitive targeting of a type II early Golgi membrane protein. Mol. Biol. Cell 8, 1073–1087.[Abstract]
Mallet, W.G., and Maxfield, F.R. (1999). Chimeric
forms of furin and TGN38 are transported with the plasma membrane in the
trans-Golgi network via distinct endosomal pathways. J. Cell
Biol. 146,
345–359.
Matter, K. Epithelial polarity: sorting out the sorters. (2000). Curr. Biol. 10, R39–R42.[CrossRef][Medline]
Nelson, W.J., and Yeaman, C. (2001). Protein trafficking in the exo-cytic pathway of polarized epithelial cells. Trends Cell Biol. 11, 483–486.[CrossRef][Medline]
Puri, S., Bachert, C., Fimmel, C.J., and Linstedt, A.D. (2002). Cycling of early Golgi proteins via the cell surface, and endosomes upon lumenal pH disruption. Traffic 3, 641–653.[CrossRef][Medline]
Puthenveedu, M.A., and Linstedt, A.D. (2001). Evidence
that Golgi structure depends on a p115 activity that is independent of the
vesicle tether components giantin and GM130. J. Cell Biol.
155,
227–238.
Rajasekaran, A.K., Humphrey, J.S., Wagner, M., Miesenbock, G., Le Bivic, A., Bonifacino, J.S., and Rodriguez-Boulan, E. (1994). TGN38 recycles basolaterally in polarized Madin-Darby canine kidney cells. Mol. Biol. Cell 5, 1093–1103.[Abstract]
Rodriguez-Boulan, E., and Gonzalez, A. (1999). Glycans in post-Golgi apical targeting: sorting signals or structural props? Trends Cell Biol. 9, 291–294.[CrossRef][Medline]
Weisz, O.A., Machamer, C.E., and Hubbard, A.L. (1992).
Rat liver dipeptidylpeptidase IV contains competing apical and basolateral
targeting information. J. Biol. Chem.
267,
22282–22288.
This article has been cited by other articles:
|
|
 |
|
  M. A. Ellis, B. A. Potter, K. O. Cresawn, and O. A. Weisz Polarized biosynthetic traffic in renal epithelial cells: sorting, sorting, everywhere Am J Physiol Renal Physiol, October 1, 2006; 291(4): F707 - F713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Natarajan and A. D. Linstedt A Cycling cis-Golgi Protein Mediates Endosome-to-Golgi Traffic Mol. Biol. Cell, November 1, 2004; 15(11): 4798 - 4806. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
