Sorting Nexins – Unifying Trends and New Perspectives

Carlton, Jeremy G.; Bujny, Miriam V.; Rutherford, Anna C.; Cullen, Peter J.

doi:10.1111/j.1600-0854.2005.00260.x

Cited by 180 publications

(162 citation statements)

References 57 publications

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“…One should be cautious to interpret data of knockdown and overexpression experiments because they often contradict. It was shown by siRNA that knockdown of SNX1 showed no effect on EGF receptor degradation (Gullapalli et al, 2004;Carlton et al, 2004) or on transferrin receptor trafficking (Carlton et al, 2004), whereas SNX1 is required for proper endosome retrieval of the CI-MPR (Carlton et al, 2005). This contrasts with the findings of previous studies using overexpression showing that overexpression of SNX1 enhances EGF receptor degradation (Kurten et al, 1996;Chin et al, 2001;Zheng et al, 2001), whereas other groups were unable to demonstrate that overexpression of SNX1 or SNX2, 3, or 4 increases the turnover of insulin or EGF receptors (Haft et al, 1998).…”

Section: Ehrab7a Overexpression Caused a Decrease Of Cp Activity Whicontrasting

confidence: 56%

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

Nakada‐Tsukui

Saito‐Nakano

Ali

et al. 2005

MBoC

139

173

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Vesicular trafficking plays an important role in a virulence mechanism of the enteric protozoan parasite Entamoeba histolytica as secreted and lysosomal cysteine protease (CP) contributes to both cytolysis of tissues and degradation of internalized host cells. Despite the primary importance of intracellular sorting in pathogenesis, the molecular mechanism of CP trafficking remains largely unknown. In this report we demonstrate that transport of CP is regulated through a specific interaction of Rab7A small GTPase (EhRab7A) with the retromerlike complex. The amoebic retromerlike complex composed of Vps26, Vps29, and Vps35 was identified as EhRab7A-binding proteins. The amoebic retromerlike complex specifically bound to GTP-EhRab7A, but not GDP-EhRab7A through the direct binding via the carboxy terminus of EhVps26. In erythrophagocytosis the retromerlike complex was recruited to prephagosomal vacuoles, the unique preparatory vacuole of digestive enzymes, and later to phagosomes. This dynamism was indistinguishable from that of EhRab7A, and consistent with the premise that the retromerlike complex is involved in the retrograde transport of putative hydrolase receptor(s) from preparatory vacuoles and phagosomes to the Golgi apparatus. EhRab7A overexpression caused enlargement of lysosomes and decrease of the cellular CP activity. The reduced CP activity was restored by the coexpression of EhVps26, implying that the EhRab7A-mediated transport of CP to phagosomes is regulated by the retromerlike complex. INTRODUCTIONRab GTPases play an essential role to regulate intracellular membrane trafficking. The compartmentalization and functions of Rab proteins are modulated at multiple layers of mechanisms including isoprenylation of the carboxy terminus, nucleotide exchange, and binding of specific effector molecules (Stenmark and Olkkonen, 2001;Takai et al., 2001;Tuvim et al., 2001). Among these modulators, effectors play key roles in the control of 7-90 Rab proteins depending on organisms from fission yeast and amoeba to mammals and plants. A variety of effectors have been identified and shown to interact with specific Rab protein. For instance, regulatory secretions of neurotransmitters from neurons or insulin from pancreatic ␤-cells are regulated by the specific interaction of Rab3 with its effectors (Jahn and Sudhof, 1999). At least four proteins, Rabphilin3, Rim1, Rim2, and Noc2, are known to bind Rab3 and recruit cAMP-GEFII, 14 -3-3, and zyxin, respectively, to regulate cAMP responsiveness, phosphoserine-dependent signaling, and the interaction with cytoskeleton (Kotake et al., 1997;Ozaki et al., 2000;Sun et al., 2003). The specificity of the Rab-effector interaction is attributable to primary sequence motifs in only a few cases including exophilins or Slip/Slac2, Rab3, and Rab27 effectors (Izumi et al., 2003). However, the majority of Rab effectors lack recognizable conserved binding motifs. For instance, Rab5 effectors, rabaptin-5, Rabex-5, EEA1, Rabenosyn-5, hVps34/p150, p110␤/p35␣, rabip4Ј, and rabankyrin-5, which a...

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Section: Ehrab7a Overexpression Caused a Decrease Of Cp Activity Whicontrasting

confidence: 56%

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

Nakada‐Tsukui

Saito‐Nakano

Ali

et al. 2005

MBoC

139

173

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“…The PtdIns phosphate-binding SNX PX domains bind to specific phospholipids so as to target individual nexins to specific membranous sites (27,28). To explore the relevance of SNX9 interaction with WASp, we examined the PtdIns-binding properties of SNX9 by probing nitrocellulose-immobilized PtdIns arrays with GST SNX9 PX domain fusion protein and immunoblotting with anti-GST antibody.…”

Section: Snx9 Associates and Colocalizes With Waspmentioning

confidence: 99%

“…Sorting nexins are a family of peripheral membrane proteins involved in endocytosis, membrane trafficking, and protein sorting (27,28) and defined by a phox (phagocyte oxidase) homology domain (PX) that mediates binding to PtdIns phosphates and consequent targeting to PtdIns-enriched membrane sites. SNX9 has been studied in human, murine, and Drosophila cells and binds directly to AP-2, clathrin, dynamin-2, Drosophila orthologue of Nck, and activated cdc42-associated kinase, localizes at the curved site of clathrin-coated pits, and modulates membrane trafficking of dynamin and clathrin-mediated endocytosis/sorting of several transmembrane receptors (29)(30)(31)(32)(33).…”

mentioning

confidence: 99%

Interaction of the Wiskott–Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells

Badour

McGavin

Zhang

et al. 2007

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

121

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The Wiskott-Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for T cell activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) in T cells and that WASp, SNX9, p85, and CD28 colocalize within clathrin-containing endocytic vesicles after TCR/CD28 costimulation. SNX9, implicated in clathrin-mediated endocytosis, binds WASp via its SH3 domain and uses its PX domain to interact with the phosphoinositol 3-kinase regulatory subunit p85 and product, phosphoinositol (3,4,5)P 3. The data reveal ligationinduced CD28 endocytosis to be clathrin-and phosphoinositol 3-kinase-dependent and TCR/CD28-evoked CD28 internalization and NFAT activation to be markedly enhanced by SNX9 overexpression, but severely impaired by expression of an SNX9 mutant (SNX9⌬PX) lacking p85-binding capacity. CD28 endocytosis and CD28-evoked actin polymerization also are impaired in WASpdeficient T cells. These findings suggest that SNX9 couples WASp to p85 and CD28 so as to link CD28 engagement to its internalization and to WASp-mediated actin remodeling required for CD28 cosignaling. Thus, the WASp/SNX9/p85/CD28 complex enables a unique interface of endocytic, actin polymerizing, and signal transduction pathways required for CD28-mediated T cell costimulation.actin cytoskeleton ͉ costimulation ͉ lymphocyte activation ͉ signaling

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“…Trafficking between these endocytic compartments is highly regulated and often involves critical sorting steps. Recently, a large family of sorting nexin (SNX) proteins characterized by the presence of Phox (PX) domains has been identified and implicated in the regulation of different steps of the endocytic pathway (4,5). For example, the founding member of the SNX family, SNX1, was identified as an interacting partner of the epidermal growth factor receptor, and overexpression of SNX1 was found to enhance lysosomal degradation of epidermal growth factor receptor (6).…”

mentioning

confidence: 99%

Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics

Zheng¹,

Tang²,

Tang

et al. 2006

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

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RGS-PX1 (also known as sorting nexin 13) is a member of both the regulator of G protein signaling (RGS) and sorting nexin (SNX) protein families. Biochemical and cell culture studies have shown that RGS-PX1͞SNX13 attenuates G␣s-mediated signaling through its RGS domain and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. To understand the functions of RGS-PX1͞SNX13 in vivo, we generated mice carrying targeted mutations of Snx13 and found that systemic Snx13-null mice were embryonic lethal around midgestation. Snx13-null embryos had significant overall growth retardation and defects in neural tube closure, blood vessel formation, and the formation of the placental labyrinthine layer. Moreover, the Snx13-null visceral yolk sac endoderm cells showed dramatic changes in the organization of endocytic compartments, abundant autophagic vacuoles, and abnormal localization of several endocytic markers, including megalin, a receptor for nutrients and proteins; ARH, a coat protein that binds megalin; LAMP2; and LC3. These changes suggest that Snx13-null embryos are defective in nutrient uptake and transport, which may contribute to the other developmental abnormalities observed. Taken together, our findings demonstrate an essential role for RGS-PX1͞SNX13 in mouse development and provide previously undescribed insights into its cellular function in the regulation of endocytosis dynamics.megalin ͉ receptor endocytosis ͉ regulator of G protein signaling ͉ visceral yolk sac endoderm R eceptor-mediated endocytosis is the process by which plasma membrane components and extracellular materials such as nutrients, hormones, antigens, and other macromolecules are selectively internalized into cytoplasmic vesicles, delivered to early and late endosomes and degraded in lysosomes or recycled back to the plasma membrane through recycling endosomes (1-3). Trafficking between these endocytic compartments is highly regulated and often involves critical sorting steps. Recently, a large family of sorting nexin (SNX) proteins characterized by the presence of Phox (PX) domains has been identified and implicated in the regulation of different steps of the endocytic pathway (4, 5). For example, the founding member of the SNX family, SNX1, was identified as an interacting partner of the epidermal growth factor receptor, and overexpression of SNX1 was found to enhance lysosomal degradation of epidermal growth factor receptor (6). More recently, knock-down of SNX1 expression by RNA interference was shown to perturb the steady state distribution of the cation-independent mannose-6-phosphate receptor (CI-MPR) from the trans-Golgi network to endosomes and to increase the degradation rate of CI-MPR, establishing a role for SNX1 in endosome-to-trans-Golgi network transport (7).RGS-PX1 (also known as SNX 13, the designation by the human gene nomenclature committee) was identified originally as a member of the regulator of G protein signaling (RGS) protein family through bioinformatics analysis (8). RGS-PX1 contains...

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Sorting Nexins – Unifying Trends and New Perspectives

Cited by 180 publications

References 57 publications

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

Interaction of the Wiskott–Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells

Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics

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