Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant

Hunziker, Walter; Harter, Cordula; Matter, Karl; Mellman, Ira

doi:10.1016/0092-8674(91)90437-4

Cited by 292 publications

(257 citation statements)

References 48 publications

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“…Very similar results have been obtained with the two basolateral sorting signals of the low density lipoprotein receptor (6). This suggests that the same sorting machinery operates in both the TGN and the endocytotic pathway, or that sorting in both pathways actually 1 The abbreviations used in this paper are: TGN, trans-Golgi network; pIgR, polymeric immunoglobulin receptor; CaM, calmodulin; d/pIgA, dimeric/polymeric immunoglobulin A; VSVG, vesicular stomatitis virus protein G; BS 3 occurs in a common compartment.…”

supporting

confidence: 62%

“…Moreover, this segment can be transplanted to a heterologous reporter molecule, which is then retargeted from the apical to the basolateral surface (2). In at least one other case, the low density lipoprotein receptor, autonomous basolateral sorting signals have been identified (3).…”

mentioning

confidence: 99%

“…Indeed, we have recently found that dIgA binding causes tyrosine phosphorylation of a phosphatidylinositol-specific phospholipase C␥1, activation of protein kinase C, and production of inositol 1,4,5-trisphosphate. 2 Transcytosis of pIgR and other molecules is stimulated either by activation of protein kinase C (10) or by increase in intracellular free Ca 2ϩ , 3 so both arms of the phospholipase C signaling pathway may redundantly stimulate transcytosis. Delivery to the apical surface, either by transcytosis or directly from the TGN, is also stimulated by the heterotrimeric G protein, G s (11,12), as well as cAMP and protein kinase A (13,14).…”

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Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

Chapin

Enrich

Aroeti

et al. 1996

Journal of Biological Chemistry

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We have identified a major calmodulin (CaM)-binding protein in rat liver endosomes using 125 I-CaM overlays from two-dimensional protein blots. Immunostaining of blots demonstrates that this protein is the polymeric immunoglobulin receptor (pIgR). We further investigated the interaction between pIgR and CaM using Madin-Darby canine kidney cells stably expressing cloned wild-type and mutant pIgR. We found that detergent-solubilized pIgR binds to CaM-agarose in a Ca 2؉ -dependent fashion, and binding is inhibited by the addition of excess free CaM or the CaM antagonist W-13 (N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide), suggesting that pIgR binding to CaM is specific. The plasma membrane of polarized epithelial cells is divided into apical and basolateral surfaces, each having a distinct protein and lipid composition. Cells use two pathways to deliver proteins to the correct surface. First, newly made proteins are packaged in the trans-Golgi network (TGN) 1 into vesicles that deliver them directly to either the apical or basolateral surface. Second, proteins can be delivered first to one surface and then endocytosed and transcytosed to the opposite surface. At least in the well polarized Madin-Darby canine kidney (MDCK) cell line, targeting to the basolateral surface generally requires a sorting signal located in the cytoplasmic domain of the protein. For a number of basolateral proteins it has been found that mutations in the cytoplasmic domain prevent TGN to basolateral targeting (1). The first basolateral signal to be identified is the 17-amino acid membrane proximal segment (residues 653-670) of the cytoplasmic domain of the polymeric immunoglobulin receptor (pIgR) (2). This protein is normally delivered from the TGN to the basolateral surface, and then endocytosed and transcytosed to the apical surface. Deletion of most of this 17-residue segment prevents TGN to basolateral delivery. Moreover, this segment can be transplanted to a heterologous reporter molecule, which is then retargeted from the apical to the basolateral surface (2). In at least one other case, the low density lipoprotein receptor, autonomous basolateral sorting signals have been identified (3).The pIgR basolateral targeting signal has been systematically analyzed by alanine scanning mutagenesis (4). Mutation of His-656, Arg-657, or Val-660 to Ala substantially diminishes, but does not eliminate, TGN to basolateral targeting. Mutation of other residues had little or no effect. The structure of a synthetic 17-residue peptide corresponding to this signal has been determined by two-dimensional nuclear magnetic resonance spectroscopy (4). This peptide tends to adopt a putative type 1 ␤-turn, encompassing residues 658 -661, followed by a nascent helical structure. In MDCK cells polarized sorting takes place in both the TGN and after endocytosis. Mutations that diminish TGN to basolateral sorting and increase TGN to apical sorting have a similar effect on sorting in the endocytotic pathway, decreasing recycling to the basolateral surface and...

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Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

Chapin

Enrich

Aroeti

et al. 1996

Journal of Biological Chemistry

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“…This example offers particularly complex possibilities for control, as binding of one ligand IGF-II leads to stimulation of GQ2 (Okamoto et al, 1990(Okamoto et al, , 1991, whereas binding of the other ligand, Man-6-P (or enzymes containing Man-6-P) can modulate the effects of IGF-II (Rogers and Hammerman, 1989). Furthermore, the postulated receptor that binds BFA also may be involved in growth control, as cells that are less sensitive to BFA (MDCK, PtKj) tend to be nontransformed cells (Hunziker et al, 1991a;Ktistakis et al, 1991).…”

Section: G Proteins and Cellular Regulation: Cross-talk Between Signamentioning

confidence: 99%

Role of heterotrimeric G proteins in membrane traffic.

Bomsel

Mostov

1992

MBoC

207

142

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“…For basolateral proteins, adaptor protein complexes AP-1B 9 and AP-4 (ref. 10) might be involved in sorting proteins in the TGN and/or endosomes [11][12][13] . Transport from the TGN to the apical plasma membrane is dependent on dynamin and a kinesin-like motor protein 14 .…”

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Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network

et al. 2004

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Protein kinase D (PKD) binds to diacylglycerol (DAG) in the trans-Golgi network (TGN) and is activated by trimeric G-protein subunits βγ. This complex then regulates the formation of transport carriers in the TGN that traffic to the plasma membrane in non-polarized cells. Here we report specificity of different PKD isoforms in regulating protein trafficking from the TGN. Kinase-inactive forms of PKD1, PKD2 and PKD3 localize to the TGN in polarized and nonpolarized cells. PKD activity is required only for the transport of proteins containing basolateral sorting information, and seems to be cargo specific.Protein kinase D1 (PKD1) is a serine/threonine kinase that binds to the TGN through its first cysteine-rich domain in a DAG-dependent process 1,2 . Kinase-inactive PKD1 (PKD-KD) induces the formation of TGN tubules containing TGN 46 and furin, proteins that cycle between the TGN and the plasma membrane 3 . Resident enzymes of the TGN, such as sialyltransferase or coat proteins of other transport carriers (COPI or clathrin), are not found in these tubules 3 . Furthermore, PKD1 is specific for the transport of proteins from the TGN to the cell surface in non-polarized cells 3 . PKD2 (ref. 4) and PKD3 (ref. 5) have been identified, but it is unknown whether different PKD isoforms have specificity for different classes of cargo proteins or are functionally redundant.The intracellular distribution and function of PKD2 were examined with glutathione Stransferase (GST)-tagged wild-type (WT) and kinase-dead (KD) proteins expressed in HeLa cells (Fig. 1). The TGN of PKD2-KD transfected cells was tubulated and contained TGN 46 ©2004 Nature Publishing Group 7 Correspondence should be addressed to V.M. (malhotra@biomail.ucsd.edu). 8 These authors contributed equally to this work. COMPETING FINANCIAL INTERESTSThe authors declare that they have no competing financial interests. NIH Public Access Author ManuscriptNat Cell Biol. Author manuscript; available in PMC 2012 June 12. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript and furin (Fig. 1c, d). Neither resident enzymes of the TGN such as sialyltransferase (Fig. 1d) nor coat proteins (COPI and clathrin; data not shown) were present in these tubules. We examined the effects of PKD2-KD expression on post-Golgi transport of ts-G-GFP (green fluorescent protein-tagged ts045 mutant vesicular stomatitis virus-G protein (VSV-G)), a well-characterized exocytic marker 6 . HeLa cells were co-transfected with cDNAs for ts-G-GFP and GST-PKD2-KD at a ratio of 1:5 (ts-G-GFP to PKD2). After incubation overnight at 4 °C, cells were shifted to 20 °C for 3 h in the presence of cycloheximide to accumulate ts-G-GFP in the TGN, and then transferred to 32 °C to allow the protein to leave the TGN. The percentage of cells (n = 500) with ts-G-GFP on the plasma membrane was quantified at different times after the shift to 32 °C. In cells expressing PKD2-WT, about 50% of the cells expressed ts-G-GFP on the plasma membrane within 10 min of the shift to 32 °C, and by 4...

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Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant

Cited by 292 publications

References 48 publications

Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

Role of heterotrimeric G proteins in membrane traffic.

Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network

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