SNX5, a New Member of the Sorting Nexin Family, Binds to the Fanconi Anemia Complementation Group A Protein

Otsuki, Tetsuya; Ozawa, Keiya; Liu, Johnson M.

doi:10.1006/bbrc.1999.1731

Cited by 61 publications

(49 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For this to be the case, 'unwanted' components would need to be sorted and segregated from those targeted to the lysosome. The sorting nexins, SNX1 and SNX5, represent promising candidates for this role in the macropinosome as they have both been implicated in the sorting and trafficking of a number of different cargo proteins (Gullapalli et al, 2006;Kurten et al, 1996;Otsuki et al, 1999;Reuter et al, 2003). By using a tubular element to remove plasma membrane components rather than a spherical vesicle, the ratio of surface area to volume in the macropinosome is reduced, effectively 'tightening the slack' on the compartment.…”

Section: Discussionmentioning

confidence: 99%

Visualisation of macropinosome maturation by the recruitment of sorting nexins

Kerr

Lindsay

Luetterforst

et al. 2006

Journal of Cell Science

131

162

View full text Add to dashboard Cite

We report that phosphoinositol-binding sorting nexin 5 (SNX5) associates with newly formed macropinosomes induced by EGF stimulation. We used the recruitment of GFP-SNX5 to macropinosomes to track their maturation. Initially, GFP-SNX5 is sequestered to discrete subdomains of the macropinosome; these subdomains are subsequently incorporated into highly dynamic, often branched, tubular structures. Time-lapse videomicroscopy revealed the highly dynamic extension of SNX5-labelled tubules and their departure from the macropinosome body to follow predefined paths towards the perinuclear region of the cell, before fusing with early endosomal acceptor membranes. The extension and departure of these tubular structures occurs rapidly over 5-10 minutes and is dependent upon intact microtubules. As the tubular structures depart from the macropinosome there is a reduction in the surface area and an increase in tension of the limiting membrane of the macropinosome. In addition to the recruitment of SNX5 to the macropinosome, Rab5, SNX1 and EEA1 are also recruited by newly formed macropinosomes, followed by the accumulation of Rab7. SNX5 forms heterodimers with SNX1 and this interaction is required for endosome association of SNX5. We propose that the departure of SNX5-positive tubules represents a rapid mechanism of recycling components from macropinosomes thereby promoting their maturation into Rab7-positive structures. Collectively these findings provide a detailed real-time characterisation of the maturation process of the macropinocytic endosome.

show abstract

Section: Discussionmentioning

confidence: 99%

Visualisation of macropinosome maturation by the recruitment of sorting nexins

Kerr

Lindsay

Luetterforst

et al. 2006

Journal of Cell Science

131

162

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

“…Subsequent studies have identified more than a dozen members of the Snx family in mammals and they have been found associated with several membrane proteins that traffic throughout the endocytic system, including the insulin receptor, the transferrin receptor and the PDGF receptor (Renfrew-Haft et al, 1998;Otsuki et al, 1999;Parks et al, 2001). SNX1 has been implicated in the down-regulation of activated EGF receptors in lysosomes and overexpression of SNX1 can lead to increased EGF receptor degradation (Kurten et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Identification of the Functional Domains of Yeast Sorting Nexins Vps5p and Vps17p

Seaman

Williams

2002

MBoC

100

View full text Add to dashboard Cite

Sorting nexins (Snxs) are a recently discovered family of conserved hydrophilic cytoplasmic proteins that have been found associated with membranes of the endocytic system and that are implicated in the trafficking of many endosomal membrane proteins, including the epidermal growth factor receptor and transferrin receptor. Snx proteins are partly defined by the presence of a p40 phox homology domain that has recently been shown to bind phosphatidylinositol 3-phosphate. Most Snx proteins also contain a predicted coiled-coils domain in the carboxyl-terminal half of the protein and have been shown to form dimers with other members of the Snx family. The yeast sorting nexins Vps5p and Vps17p form a dimer and are also components of the retromer complex that mediates endosome-to-Golgi transport of the carboxypeptidase Y receptor Vps10p. To functionally define the different domains of the yeast sorting nexins Vps5p and Vps17p, we have generated various truncations to examine the role that the different domains of Vps5p/ Vps17p play in their respective functions. Herein, we show that the C-terminal halves of Vps5p and Vps17p, which contain the coiled-coils domains, are necessary and sufficient for their interaction. We have also mapped the retromer assembly domain to the N-terminal half of Vps5p and found that binding of Vps5p by Vps17p synergizes the interaction between Vps5p and other retromer components. Additionally, we have examined which domain(s) of Vps5p is necessary for membrane association.

show abstract

SNX5, a New Member of the Sorting Nexin Family, Binds to the Fanconi Anemia Complementation Group A Protein

Cited by 61 publications

References 23 publications

Visualisation of macropinosome maturation by the recruitment of sorting nexins

Visualisation of macropinosome maturation by the recruitment of sorting nexins

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

Identification of the Functional Domains of Yeast Sorting Nexins Vps5p and Vps17p

Contact Info

Product

Resources

About