A New Member of the Sorting Nexin Family Interacts with the C-Terminus of P-Selectin

Florian, Volker; Schlüter, Thomas; Bohnensack, Ralf

doi:10.1006/bbrc.2001.4467

Cited by 41 publications

(39 citation statements)

References 25 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interaction of SNX17 with the cytoplasmic domain of Pselectin was recently demonstrated, indicating that SNX17 may regulate the traffic and\or function of P-selectin [154].…”

Section: Membrane Trafficmentioning

confidence: 99%

The Phox homology (PX) domain, a new player in phosphoinositide signalling

Seet

Hanson

et al. 2001

Biochemical Journal

View full text Add to dashboard Cite

Phosphoinositides are key regulators of diverse cellular processes. The pleckstrin homology (PH) domain mediates the action of PtdIns(3,4)P # , PtdIns(4,5)P # and PtdIns(3,4,5)P $ , while the FYVE domain relays the pulse of PtdIns3P. The recent establishment that the Phox homology (PX) domain interacts with PtdIns3P and other phosphoinositides suggests another mechanism by which phosphoinositides can regulate\integrate multiple cellular events via a spectrum of PX domain-containing proteins.

show abstract

“…Interaction of SNX17 with the cytoplasmic domain of Pselectin was recently demonstrated, indicating that SNX17 may regulate the traffic and\or function of P-selectin [154].…”

Section: Membrane Trafficmentioning

confidence: 99%

The Phox homology (PX) domain, a new player in phosphoinositide signalling

Seet

Hanson

et al. 2001

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…The sorting nexins are a family of trafficking molecules defined by the presence of a Phox homology (PX) domain (for recent reviews, see [18][19][20]). Originally identified in the p40phox and the p47phox subunit of NADPH oxidase, the *120-amino acid PX domain has been subsequently recognized in a number of proteins including sorting nexins and signaling molecules such as phosphatidylinositol 3-kinase (PI 3-kinase) and cytokine-independent survival kinase (CISK) [21][22][23][24][25][26][27][28][29][30][31][32][33]. The PX domain has also been characterized as a phosphoinositide-binding module that can localize both the host protein and a bound protein to the cell membrane or intracellular vesicles (for reviews, see [20,[34][35][36]).…”

Section: Introductionmentioning

confidence: 99%

SLIC‐1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL‐1

Schaff¹,

Shih²,

Lorenz³

et al. 2008

Eur J Immunol

View full text Add to dashboard Cite

P-Selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of leukocytes that serves as the major ligand for the selectin family of adhesion molecules and functions in leukocyte tethering and rolling on activated endothelium and platelets. Previous studies have implicated the highly conserved cytoplasmic domain of PSGL-1 in regulating outside-in signaling of integrin activation. However, molecules that physically and functionally interact with this domain are not completely defined. Using a yeast two-hybrid screen with the cytoplasmic domain of PSGL-1 as bait, a novel protein designated selectin ligand interactor cytoplasmic-1 (SLIC-1) was isolated. Computer-based homology search revealed that SLIC-1 was the human orthologue for the previously identified mouse sorting nexin 20. Direct interaction between SLIC-1 and PSGL-1 was specific as indicated by co-immunoprecipitation and motif mapping. Colocalization experiments demonstrated that SLIC-1 contains a Phox homology domain that binds phosphoinositides and targets the PSGL-1/SLIC-1 complex to endosomes. Deficiency in the murine homologue of SLIC-1 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1. We conclude that SLIC-1 serves as a sorting molecule that cycles PSGL-1 into endosomes with no impact on leukocyte recruitment.Supporting Information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2008/37777_s.pdf IntroductionThe initial tethering and rolling of leukocytes on activated endothelium and platelets is a key biological event mediated by P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein that functions as a unique high-affinity ligand for the selectin family of adhesion molecules (for reviews, see [1][2][3][4]). Structurally, PSGL-1 is a type I integral membrane protein consisting of an N-terminal selectin-binding domain followed by a region of multiple decameric repeats bearing O-linked glycans, a short transmembrane domain, and lastly a cytoplasmic tail [5][6][7][8][9][10]. Comparison of human and murine PSGL-1 reveals that the 69-amino acid intracellular domain of PSGL-1 is highly conserved. While overall identity between human and Abbreviations: EEA-1: early endosomal antigen-1 Á EGFP: enhanced green fluorescent protein Á ERM: ezrin/radixin/ moesin Á L-E/I: L cell monolayer expressing E-selectin and ICAM-1 Á PI: phosphatidylinositol Á PI 3-kinase: phosphatidylinositol 3-kinase Á PSGL-1: P-selectin glycoprotein ligand-1 Á PtdIns(3)P: phosphatidylinositol 3-phosphate Á PtdIns(3,4)P 2 : phosphatidylinositol 3,4-bisphosphate Á PtdIns(3,4,5)P 3 : phosphatidylinositol 3,4,5-trisphosphate Á PX domain: phox homology domain Á SLIC-1: selectin ligand interactor cytoplasmic-1 Á SNX20: sorting nexin 20 Á TM: transmembrane Ulrich Y. Schaff et al.

show abstract

“…SNX17 is a member of the Phox-homology (PX) domain-containing protein family and has been shown to be a critical regulator of endosomal sorting and cell-surface recycling of several essential cargo molecules. These include P-selectin (6)(7)(8), amyloid precursor protein (APP) (9,10), integrins (11,12), and members of the LDL receptor family (13)(14)(15)(16)(17) via recognition of an NPxY or alternative NxxY signal. The PX proteins [often called "sorting nexins" (SNXs)] are a large family of molecules that govern diverse endosomal trafficking and signaling processes and, by definition, possess a phosphoinositide lipid-binding PX domain that promotes membrane recruitment (18)(19)(20).…”

mentioning

confidence: 99%

Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins

Ghai

Bugarčić

Liu

et al. 2013

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

125

151

View full text Add to dashboard Cite

Transit of proteins through the endosomal organelle following endocytosis is critical for regulating the homeostasis of cell-surface proteins and controlling signal transduction pathways. However, the mechanisms that control these membrane-transport processes are poorly understood. The Phox-homology (PX) domain-containing proteins sorting nexin (SNX) 17, SNX27, and SNX31 have emerged recently as key regulators of endosomal recycling and bind conserved Asn-Pro-Xaa-Tyr-sorting signals in transmembrane cargos via an atypical band, 4.1/ezrin/radixin/moesin (FERM) domain. Here we present the crystal structure of the SNX17 FERM domain bound to the sorting motif of the P-selectin adhesion protein, revealing both the architecture of the atypical FERM domain and the molecular basis for recognition of these essential sorting sequences. We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins.endosome | protein crystallography | X-ray scattering | membrane trafficking T he cell-surface levels of signaling and adhesion receptors, nutrient transporters, ion channels, and many other proteins are tightly regulated by opposing endocytic, exocytic, and endosomal recycling transport pathways. The selective sorting of these transmembrane proteins is the consequence of their interaction with essential adaptor proteins via conserved motifs present in their cytosolic tails, generally based on short linear amino acid sequences such as the Yxxϕ, DxxLL, and [DE]xxxL [LI] motifs (where ϕ is any bulky hydrophobic side-chain, and x is any residue) recognized by clathrin adaptors (1-3). The first identified sorting signal was the Asn-Pro-Xaa-Tyr (NPxY) motif, initially described in the LDL receptor (LDLR) isolated from patients suffering from familial hypercholesterolemia, where mutation of the sequence results in defective internalization and cholesterol uptake (4). The recent structure of the autosomal recessive hypercholesterolemia protein (ARH) phosphotyrosinebinding (PTB) domain in complex with the LDLR intracellular domain (ICD) provides the molecular basis of LDLR recognition and internalization within clathrin-coated pits by endocytic adaptor proteins (5).Although little is known about the sorting sequences and mechanisms required for competing endosome-to-cell surface recycling pathways, emerging evidence shows that the NPxY motif not only is vital to internalization but also aids cargo recycling via organelle-specific recognition by the endosomal protein, sorting nexin 17 (SNX17). SNX17 is a member of the Phox-homology (PX) domain-containing protein family and has been shown to be a critical regulator of endosomal sorting and cell-surface recycling of several essential cargo molecules. These include P-selectin (6-8), amyloid precursor protein (APP) (9, 10), integrins (11,12), and members of the LDL receptor family (13-17) ...

show abstract

A New Member of the Sorting Nexin Family Interacts with the C-Terminus of P-Selectin

Cited by 41 publications

References 25 publications

The Phox homology (PX) domain, a new player in phosphoinositide signalling

The Phox homology (PX) domain, a new player in phosphoinositide signalling

SLIC‐1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL‐1

Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins

Contact Info

Product

Resources

About