Endosomal SNARE proteins regulate CFTR activity and trafficking in epithelial cells

Bilan, Frédéric; Nacfer, Magali; Fresquet, Fleur; Norez, Caroline; Melin, Patricia; Martin-Berge, Alice; Beauregard, Marie-Alyette Costa de; Becq, Frédéric; Kitzis, Alain; Thoreau, Vincent

doi:10.1016/j.yexcr.2008.04.012

Cited by 26 publications

(24 citation statements)

References 43 publications

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“…It is possible that oatp1a1 phosphorylation alters this interaction, resulting in reduced plasma membrane localization. Several studies have described complexes of proteins, including syntaxin 16, small GTPases such as Sar1 and Arf1, and PDZ domain proteins such as NHERF-1 and PDZK1, that regulate trafficking and subcellular localization of CFTR (3,16). The high-density lipoprotein receptor scavenger receptor class B, type I (SR-BI), also binds to PDZK1 through its COOH terminus (19,34), and this interaction is required for trafficking of SR-BI to the cell surface (34).…”

Section: Discussionmentioning

confidence: 99%

PDZK1 binding and serine phosphorylation regulate subcellular trafficking of organic anion transport protein 1a1

Choi

Murray

Wolkoff

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Although perturbation of organic anion transport protein (oatp) cell surface expression can result in drug toxicity, little is known regarding mechanisms regulating its subcellular distribution. Many members of the oatp family, including oatp1a1, have a COOH-terminal PDZ consensus binding motif that interacts with PDZK1, while serines upstream of this site (S634 and S635) can be phosphorylated. Using oatp1a1 as a prototypical member of the oatp family, we prepared plasmids in which these serines were mutated to glutamic acid [E634E635 (oatp1a1(EE)), phosphomimetic] or alanine [A634A635 (oatp1a1(AA)), nonphosphorylatable]. Distribution of oatp1a1(AA) and oatp1a1(EE) was largely intracellular in transfected human embryonic kidney (HEK) 293T cells. Cotransfection with a plasmid encoding PDZK1 revealed that oatp1a1(AA) was now expressed largely on the cell surface, while oatp1a1(EE) remained intracellular. To quantify these changes, studies were performed in HuH7 cells stably transfected with these oatp1a1 plasmids. These cells endogenously express PDZK1. Surface biotinylation at 4°C followed by shift to 37°C showed that oatp1a1(EE) internalizes quickly compared with oatp1a1(AA). To examine a physiological role for phosphorylation in oatp1a1 subcellular distribution, studies were performed in rat hepatocytes exposed to extracellular ATP, a condition that stimulates serine phosphorylation of oatp1a1 via activity of a purinergic receptor. Internalization of oatp1a1 under these conditions was rapid. Thus, although PDZK1 binding is required for optimal cell surface expression of oatp1a1, phosphorylation provides a mechanism for fast regulation of the distribution of oatp1a1 between the cell surface and intracellular vesicular pools. Identification of the proteins and motor molecules that mediate these trafficking events represents an important area for future study.

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Section: Discussionmentioning

confidence: 99%

PDZK1 binding and serine phosphorylation regulate subcellular trafficking of organic anion transport protein 1a1

Choi

Murray

Wolkoff

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…regulated trafficking of CFTR in native airway epithelial cells (9). Other studies identified interactions of the endosomal SNARE proteins syntaxin 7 and 8 (but not syntaxin 3) with CFTR that modulated trafficking and function (10,11). The failure to identify a CFTR-syntaxin 3 interaction and a role for syntaxin 3 trafficking in airway epithelial cells further supports the notion that apical trafficking directs CFTR function in native epithelia through its interaction with cell-specific proteins in the same manner that syntaxins display isoform specificity in regulation of exocytosis in epithelial cells (27,33,48,50).…”

Section: Discussionmentioning

confidence: 99%

Syntaxin 3 is necessary for cAMP- and cGMP-regulated exocytosis of CFTR: implications for enterotoxigenic diarrhea

Collaco

Marathe

Kohnke

et al. 2010

American Journal of Physiology-Cell Physiology

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Enterotoxins elaborated by Vibrio cholerae and Escherichia coli cannot elicit fluid secretion in the absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. After enterotoxin exposure, CFTR channels are rapidly recruited from endosomes and undergo exocytic insertion into the apical plasma membrane of enterocytes to increase the number of channels on the cell surface by at least fourfold. However, the molecular machinery that orchestrates exocytic insertion of CFTR into the plasma membrane is largely unknown. The present study used immunofluorescence, immunoblotting, surface biotinylation, glutathione S-transferase (GST) pulldown assays, and immunoprecipitation to identify components of the exocytic soluble N-ethylmaleimide (NEM)-sensitive factor attachment receptor (SNARE) vesicle fusion machinery in cyclic nucleotide-activated exocytosis of CFTR in rat jejunum and polarized intestinal Caco-2(BB)e cells. Syntaxin 3, an intestine-specific SNARE, colocalized with CFTR on the apical domain of enterocytes in rat jejunum and polarized Caco-2(BB)e cells. Coimmunoprecipitation and GST binding studies confirmed that syntaxin 3 interacts with CFTR in vivo. Moreover, heat-stable enterotoxin (STa) activated exocytosis of both CFTR and syntaxin 3 to the surface of rat jejunum. Silencing of syntaxin 3 by short hairpin RNA (shRNA) interference abrogated cyclic nucleotide-stimulated exocytosis of CFTR in cells. These observations reveal a new and important role for syntaxin 3 in the pathophysiology of enterotoxin-elicited diarrhea.

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“…The entire endosomal SNARE complex has been reported to interact with the CFTR chloride channel and to reduce its surface expression (Bilan et al. , 2004, 2008; Tang et al. , 2011), but the underlying molecular mechanisms have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1

Renigunta

Fischer

Zuzarte

et al. 2014

MBoC

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Endosomal SNARE proteins regulate CFTR activity and trafficking in epithelial cells

Cited by 26 publications

References 43 publications

PDZK1 binding and serine phosphorylation regulate subcellular trafficking of organic anion transport protein 1a1

PDZK1 binding and serine phosphorylation regulate subcellular trafficking of organic anion transport protein 1a1

Syntaxin 3 is necessary for cAMP- and cGMP-regulated exocytosis of CFTR: implications for enterotoxigenic diarrhea

Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1

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