Sorting Nexin 27 Protein Regulates Trafficking of a p21-activated Kinase (PAK) Interacting Exchange Factor (β-Pix)-G Protein-coupled Receptor Kinase Interacting Protein (GIT) Complex via a PDZ Domain Interaction

Valdes, Julie L.; Tang, Jingrong; McDermott, Mark I.; Kuo, Jean Cheng; P., Zimmerman, Seth; Wincovitch, Stephen; Waterman‐Storer, Clare M.; Milgram, Sharon L.; Playford, Martin P.

doi:10.1074/jbc.m111.260802

Cited by 43 publications

(60 citation statements)

References 45 publications

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“…SNX27, however, possesses a unique PDZ domain involved in alternative cargo trafficking (Cai et al, 2011;Gallon et al, 2014;Lauffer et al, 2010;Lunn et al, 2007;Steinberg et al, 2013;Temkin et al, 2011;Valdes et al, 2011;Wang et al, 2013), and our results now suggest an additional unique property of this protein with respect to lipid headgroup association, such that it interacts with PtdInsP species not bound by the other family members. Sequence analyses of the PX-FERM proteins highlight positively charged residues found exclusively in SNX27, which are structurally predicted to form a contiguous basic surface on the F3 module, and we find this pocket is required for the differing PtdInsP-binding specificities of the protein.…”

Section: Discussionmentioning

confidence: 61%

“…Previous studies have shown that the PX domain of these proteins binds with high specificity to PtdIns3P, driving their localization to PtdIns3P-enriched early endosomes Stockinger et al, 2002). PX-FERM proteins can then interact with cargo containing NPxY or NxxY motifs, and also PDZ-binding motif (PDZbm) cargo, in the case of SNX27, at the early endosomal membrane (Balana et al, 2011;Bottcher et al, 2012;Cai et al, 2011;Ghai et al, 2013;Hayashi et al, 2012;Joubert et al, 2004;Knauth et al, 2005;Lauffer et al, 2010;Lunn et al, 2007;Steinberg et al, 2013;Temkin et al, 2011;Valdes et al, 2011;Wang et al, 2013). This influences the routing of transmembrane cargo trafficking, away from degradative late endosomes and into recycling and retrieval pathways from the endosome back to the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

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Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells

Ghai

Tello-Lafoz

Norwood

et al. 2014

Journal of Cell Science

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Sorting nexin 27 (SNX27) controls the endosomal-to-cell-surface recycling of diverse transmembrane protein cargos. Crucial to this function is the recruitment of SNX27 to endosomes which is mediated by the binding of phosphatidylinositol-3-phosphate (PtdIns3P) by its phox homology (PX) domain. In T-cells, SNX27 localizes to the immunological synapse in an activation-dependent manner, but the molecular mechanisms underlying SNX27 translocation remain to be clarified. Here, we examined the phosphoinositide-lipid-binding capabilities of full-length SNX27, and discovered a new PtdInsPbinding site within the C-terminal 4.1, ezrin, radixin, moesin (FERM) domain. This binding site showed a clear preference for bi-and tri-phosphorylated phophoinositides, and the interaction was confirmed through biophysical, mutagenesis and modeling approaches. At the immunological synapse of activated T-cells, cell signaling regulates phosphoinositide dynamics, and we find that perturbing phosphoinositide binding by the SNX27 FERM domain alters the SNX27 distribution in both endosomal recycling compartments and PtdIns(3,4,5)P 3 -enriched domains of the plasma membrane during synapse formation. Our results suggest that SNX27 undergoes dynamic partitioning between different membrane domains during immunological synapse assembly, and underscore the contribution of unique lipid interactions for SNX27 orchestration of cargo trafficking.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells

Ghai

Tello-Lafoz

Norwood

et al. 2014

Journal of Cell Science

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“…Two 5Ј-phosphorylated oligonucleotides (AAAGAAACAGTGGAGATATTCAATAAT-AGTGAAGCCACAGATGTATTATTGAATATCTCCACTG-TTGG and AATTCCAACAGTGGAGATATTCAATAA-TACATCTGTGGCTTCACTATTATTGAATATCTCCAC-TGTTT) were annealed and ligated into BbsI and EcoRI-cut pFIV-mCherry. Other constructs used here have been described (17,(53)(54)(55).…”

Section: Methodsmentioning

confidence: 99%

“…3B), consistent with the immunoprecipitation and colocalization studies. We then used well characterized SNX27 mutants (53) to define further the structural elements of the SNX27-PTHR interaction. HEK293 cells stably expressing HA-PTHR were transfected with wild-type SNX27 or with deletion mutants lacking either the PDZ (SNX27⌬PDZ) or FERM (SNX27⌬FERM) domains (Fig.…”

Section: Pthr Interacts With Snx27 In Earlymentioning

confidence: 99%

Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling

McGarvey¹,

Xiao²,

Bowman³

et al. 2016

Journal of Biological Chemistry

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The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domaincontaining proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor.

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“…Elucidating the mechanism of receptor sorting mediated by SNX27 will not only further our understanding AMPAR-mediated changes in synaptic plasticity, but may ultimately shed light on the molecular mechanisms that govern learning. membrane (14)(15)(16)(17)(18). The PDZ domain is a protein interaction module recognizing short amino acid motifs found at the C termini of several synaptic targets.…”

mentioning

confidence: 99%

Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs

Hussain

Diering

Sole

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

100

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Activity-dependent changes in synaptic strength have long been postulated as cellular correlates of learning and memory. Long-term potentiation (LTP), a well characterized form of synaptic plasticity, is often expressed as an increase in the number of postsynaptic AMPAtype glutamate receptors (AMPARs). Although the precise molecular mechanisms governing LTP remain elusive, this study identifies one member of the sorting nexin family, Sorting Nexin 27 (SNX27), as a critical component in this process. The ability of sorting nexins to bind specific phospholipids as well as their propensity to form protein-protein complexes, points to a role for these proteins in membrane trafficking and protein sorting. Here, we demonstrate that SNX27 binds to AMPARs, and that this interaction is regulated in an activity-dependent manner. Furthermore, we provide evidence that SNX27 is synaptically enriched and its level of expression regulates targeting of AMPARs to the neuronal surface. Loss of SNX27 abolishes recruitment of surface AMPARs during chemical LTP. Collectively, our data suggest a role for SNX27 in modulating synaptic plasticity through regulated interaction with AMPARs.PX domain | postsynaptic density | proteomics | PDZ-domain

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Sorting Nexin 27 Protein Regulates Trafficking of a p21-activated Kinase (PAK) Interacting Exchange Factor (β-Pix)-G Protein-coupled Receptor Kinase Interacting Protein (GIT) Complex via a PDZ Domain Interaction

Cited by 43 publications

References 45 publications

Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells

Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells

Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling

Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs

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