Regulation of Albumin Endocytosis by PSD95/Dlg/ZO-1 (PDZ) Scaffolds

Hryciw, Deanne H.; Ekberg, Jenny; Ferguson, Charles; Lee, Aven; Wang, Dongsheng; Parton, Robert G.; Pollock, Carol; Yun, Chris; Poronnik, Philip

doi:10.1074/jbc.m512559200

Cited by 55 publications

(41 citation statements)

References 57 publications

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“…This tethering also reduces the lateral mobility in the cell membrane of these proteins by anchoring the complex to the underlying actin cytoskeleton via accessory proteins such as ezrin, which is highly expressed in gastric epithelia (51). It has already been shown that NHERF-2 is important for the trafficking of membrane transporters such as NHE3 (47) and ion channels such as ClC-5 and TRPV5 (39,52). We have recently also shown that NHERF-1 and NHERF-2 differentially regulate albumin uptake in renal proximal tubule cells by mechanisms that involve altering the cell-surface levels of ClC-5 in different domains of the apical membrane (39).…”

Section: Discussionmentioning

confidence: 91%

“…For the experiments to silence NHERF-2, HT-29 cells were transfected with plasmids encoding siRNA directed against two different regions of NHERF-2 (Shag-274 and Shag-361) or control (Shag-FF). These plasmids have been shown previously to effectively suppress the endogenous levels of NHERF-2 (38,39). All experiments were performed 48-h post-transfection.…”

Section: Methodsmentioning

confidence: 99%

“…We hypothesized that silencing NHERF-2 would therefore prevent the translocation of PMCA to the membrane. HT-29 cells were transfected with silencing constructs (Shag-274 and Shag-361) directed against two different regions of NHERF-2 or empty vector control (Shag-FF) (39). Both silencing constructs caused a significant decrease in endogenous NHERF-2 protein to 57 Ϯ 5% and 54 Ϯ 6% for Shag-274 and 361, respectively (n ϭ 4; **, p Ͻ 0.01) compared with the Shag-FF control (Fig.…”

Section: Trafficking Of Pmca In Response To Muscarinic Stimulation Ismentioning

confidence: 99%

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Muscarinic-induced Recruitment of Plasma Membrane Ca2+-ATPase Involves PSD-95/Dlg/Zo-1-mediated Interactions

Kruger

Chen

Monteith

et al. 2009

Journal of Biological Chemistry

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Efflux of cytosolic Ca2؉ mediated by plasma membrane Ca 2؉ -ATPases (PMCA) plays a key role in fine tuning the magnitude and duration of Ca 2؉ signaling following activation of G-protein-coupled receptors. However, the molecular mechanisms that underpin the trafficking of PMCA to the membrane during Ca 2؉ signaling remain largely unexplored in native cell models. One potential mechanism for the recruitment of proteins to the plasma membrane involves PDZ interactions. In this context, we investigated the role of PMCA interactions with the Na ؉ /H ؉ exchanger regulatory factor 2 (NHERF-2) during muscarinicinduced Ca 2؉ mobilization in the HT-29 epithelial cell line. GST pull-downs in HT-29 cell lysates showed that the PDZ2 module of NHERF-2 bound to the PDZ binding motif on the C terminus of PMCA. Co-immunoprecipitations confirmed that PMCA1b and NHERF-2 associated under normal conditions in HT-29 cells. Cell surface biotinylations revealed significant increases in membrane-associated NHERF-2 and PMCA within 60 s following muscarinic activation, accompanied by increased association of the two proteins as seen by confocal microscopy. The recruitment of NHERF-2 to the membrane preceded that of PMCA, suggesting that NHERF-2 was involved in nucleating an efflux complex at the membrane. The muscarinic-mediated translocation of PMCA was abolished when NHERF-2 was silenced, and the rate of relative Ca 2؉ efflux was also reduced. These experiments also uncovered a NHERF-2-independent PMCA retrieval mechanism. Our findings describe rapid agonist-induced translocation of PMCA in a native cell model and suggest that NHERF-2 plays a key role in scaffolding and maintaining PMCA at the cell membrane.

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Section: Discussionmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Trafficking Of Pmca In Response To Muscarinic Stimulation Ismentioning

confidence: 99%

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Muscarinic-induced Recruitment of Plasma Membrane Ca2+-ATPase Involves PSD-95/Dlg/Zo-1-mediated Interactions

Kruger

Chen

Monteith

et al. 2009

Journal of Biological Chemistry

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“…Increased receptor internalization could simply increase the speed of receptor trafficking, resulting in earlier degradation and localization in the lysosome. Furthermore, many published reports demonstrate that PDZ ligand-PDZ domain containing protein interactions facilitate plasma membrane localization (40,41,61,62). Interruption of this interaction has been shown to allow faster internalization of ligand-stimulated receptor (40,61).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have demonstrated that knockdown of specific PDZ domain containing proteins results in increased internalization of receptors subsequent to ligand stimulation (40,41). Because an increased rate of internalization of the CXCR2 352T mutant could explain the increased degradation and earlier lysosome co-localization as compared FIGURE 1.…”

Section: Cooh-terminal Pdz Ligand Deletion Has No Effect On Either Rementioning

confidence: 99%

The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis

Baugher

Richmond

2008

Journal of Biological Chemistry

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Adaptor protein interaction with specific peptide motifs found within the intracellular, carboxyl terminus of chemokine receptor CXCR2 has been shown to modulate intracellular trafficking and receptor function. Efficient ligand-induced internalization of this receptor is dependent on the binding of adaptor protein 2 to the specific LLKIL motif found within the carboxyl terminus (1). In this study we show that the carboxylterminal type 1 PDZ ligand motif (-STTL) of CXCR2 plays an essential role in both proper intracellular receptor trafficking and efficient cellular chemotaxis. First, we show that CXCR2 is sorted to and degraded in the lysosome upon long-term ligand stimulation. We also show that receptor degradation is not dependent upon receptor ubiquitination, but is instead modulated by the carboxyl-terminal type I PDZ ligand of CXCR2. Deletion of this ligand results in increased degradation, earlier co-localization with the lysosome, and enhanced sorting to the Rab7-positive late endosome. We also show that deletion of this ligand effects neither receptor internalization nor receptor recycling. Furthermore, we demonstrate that deletion of the PDZ ligand motif results in impaired chemotactic response. The data presented here demonstrate that the type I PDZ ligand of CXCR2 acts to both delay lysosomal sorting and facilitate proper chemotactic response.The chemokine receptor CXCR2 is a seven transmembrane G protein-coupled receptor (GPCR) 2 that plays an important role in many diverse physiological processes such as leukocyte chemotaxis, wound healing, angiogenesis, and inflammation (see Ref. 2 for review). Conversely, CXCR2 disregulation has been linked to several pathologies, including chronic inflammation responses, metastatic progression, and aberrant angiogenesis during tumor progression (see Ref. 3 for review). However, the molecular mechanisms regulating the activation, signaling, desensitization, and resensitization of this receptor remain poorly characterized.Upon ligand engagement of CXCR2, two interrelated processes occur: a conformational change that initiates several signal transduction cascades linked to cell motility and proliferation, and a phosphorylation event that facilitates the binding of adaptor proteins essential for receptor endocytosis and subsequent intracellular trafficking (see Ref. 4 for review). Like many GPCRs, CXCR2 undergoes clathrin-mediated endocytosis subsequent to agonist-induced activation by its cognate ligands that include CXCL1-3 and 5-8 (5-7). This endocytic event initiates intracellular trafficking of the receptor that results in either a re-localization of the receptor on the plasma membrane, or a down-regulation and degradation of internalized receptor (8). Intracellular trafficking plays an essential role in the regulation of signaling and reactivation, and thereby represents a mechanism that regulates proper cellular response. The interruption of this process can result in the disregulation of both signaling and functional outcomes.Subsequent to interaction with...

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Cell Biology and Physiology of CLC Chloride Channels and Transporters

Stauber

Weinert

Jentsch

2012

Comprehensive Physiology

134

138

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Proteins of the CLC gene family assemble to homo‐ or sometimes heterodimers and either function as Cl – channels or as Cl – /H + ‐exchangers. CLC proteins are present in all phyla. Detailed structural information is available from crystal structures of bacterial and algal CLCs. Mammals express nine CLC genes, four of which encode Cl – channels and five 2Cl – /H + ‐exchangers. Two accessory β‐subunits are known: (1) barttin and (2) Ostm1. ClC‐Ka and ClC‐Kb Cl – channels need barttin, whereas Ostm1 is required for the function of the lysosomal ClC‐7 2Cl – /H + ‐exchanger. ClC‐1, ‐2, ‐Ka and ‐Kb Cl – channels reside in the plasma membrane and function in the control of electrical excitability of muscles or neurons, in extra‐ and intracellular ion homeostasis, and in transepithelial transport. The mainly endosomal/lysosomal Cl – /H + ‐exchangers ClC‐3 to ClC‐7 may facilitate vesicular acidification by shunting currents of proton pumps and increase vesicular Cl – concentration. ClC‐3 is also present on synaptic vesicles, whereas ClC‐4 and ‐5 can reach the plasma membrane to some extent. ClC‐7/Ostm1 is coinserted with the vesicular H + ‐ATPase into the acid‐secreting ruffled border membrane of osteoclasts. Mice or humans lacking ClC‐7 or Ostm1 display osteopetrosis and lysosomal storage disease. Disruption of the endosomal ClC‐5 Cl – /H + ‐exchanger leads to proteinuria and Dent's disease. Mouse models in which ClC‐5 or ClC‐7 is converted to uncoupled Cl – conductors suggest an important role of vesicular Cl – accumulation in these pathologies. The important functions of CLC Cl – channels were also revealed by human diseases and mouse models, with phenotypes including myotonia, renal loss of salt and water, deafness, blindness, leukodystrophy, and male infertility. © 2012 American Physiological Society. Compr Physiol 2:1701‐1744, 2012.

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Regulation of Albumin Endocytosis by PSD95/Dlg/ZO-1 (PDZ) Scaffolds

Cited by 55 publications

References 57 publications

Muscarinic-induced Recruitment of Plasma Membrane Ca2+-ATPase Involves PSD-95/Dlg/Zo-1-mediated Interactions

Muscarinic-induced Recruitment of Plasma Membrane Ca2+-ATPase Involves PSD-95/Dlg/Zo-1-mediated Interactions

The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis

Cell Biology and Physiology of CLC Chloride Channels and Transporters

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