Disease relevance of SNX9

• EspF of enteropathogenic Escherichia coli binds sorting nexin 9 [1].

High impact information on SNX9

• In vitro assays confirmed that recombinant SDP1 hydrolyzes triacylglycerols and diacylglycerols but not monoacylglycerols, phospholipids, galactolipids, or cholesterol esters [2].
• 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) [3].
• Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells [3].
• SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis [4].
• Transferrin internalization is inhibited in HeLa cells after siRNA-mediated knockdown of SNX9 [4].

Biological context of SNX9

• Phosphorylation of SNX9 released aldolase from the native cytosolic complex and rendered SNX9 competent for membrane binding [5].
• RNA interference experiments confirmed that SNX9 functions as a mediator of Dyn2 recruitment to membranes in cells [5].
• In order to investigate SNX9 further we have made use of a novel in vivo biotinylation system to label various GST-SH3 domains and perform blot overlays, thereby identifying synaptojanin-1 as a partner for SNX9 [6].
• Thus, our results establish that SNX9 is required for efficient clathrin-mediated endocytosis and suggest that it functions to regulate dynamin activity [4].
• Quantitative multiplex polymerase chain reaction analysis of 10 sequence-tagged sites further refined the putative TS-gene-containing region to a 2.6 Mb interval between TIAM2 and SNX9 [7].

Anatomical context of SNX9

• We show here that the complex can be activated for membrane binding of SNX9 and Dyn2 by incubation of cytosol in the presence of ATP [5].
• The results suggest that SNX9 may be recruited together with dynamin-2 and become co-assembled with AP-2 and clathrin at the plasma membrane [8].
• We previously found that SNX9 is one of the major proteins in hematopoietic cells that binds to the alpha and beta2-appendages of adaptor protein complex 2 (AP-2), a protein with a critical role in the formation of clathrin-coated vesicles at the plasma membrane [8].
• SNX9 recruits dynamin to the plasma membrane and promotes its GTPase activity, resulting in membrane constriction and ultimate transport vesicle scission [9].
• SNX9 had a cytosolic and punctate distribution, consistent with endosomal and cytosolic localization, in 3T3L1 adipocytes [10].

Associations of SNX9 with chemical compounds

• Aldolase bound with high affinity to a tryptophan-containing acidic sequence in SNX9 located close to its Phox homology domain, thereby blocking the membrane binding activity of SNX9 [5].
• Sorting nexin 9 (SNX9) belongs to a family of proteins, the sorting nexins, that are characterized by the presence of a subclass of the phosphoinositide-binding phox domain [8].
• The interaction occurs between a proline-rich domain of ACK2 and the Src homology 3 domain (SH3) of SH3PX1 [11].
• Dimerization is required for SH3PX1 tyrosine phosphorylation in response to epidermal growth factor signalling and interaction with ACK2 [12].
• The total flavonoid recovery was around 80%, and it was practically not affected by the SDP1, SDP2, and SDP3 compositions [13].

Physical interactions of SNX9

• In the cytosol, SNX9 is present in a 14.5 S complex containing dynamin-2 and an unidentified 41-kDa protein [8].

Co-localisations of SNX9

• In HeLa cells, SNX9 co-localized with both AP-2 and dynamin-2 at the plasma membrane or on vesicular structures derived from it but not with the early endosomal marker EEA1 or with AP-1 [8].

Regulatory relationships of SNX9

• The results suggest that SNX9-dependent recruitment of Dyn2 to the membrane is regulated by an interaction between SNX9 and aldolase [5].
• Microinjection of 3T3L1 cells with an antibody against SNX9 inhibited stimulation by insulin of GLUT4 translocation [10].

Other interactions of SNX9

• Insulin induced movement of SNX9 to membrane fractions from the cytosol [10].
• Two of these, Pacsin 3 and Sorting Nexin 9, were confirmed by immunoprecipitation [14].
• Truncation of as little as 13 amino acid residues at the very C-terminus in the coiled-coil/BAR domain of SH3PX1 resulted in no dimerization, no ACK2-catalysed and EGF-stimulated tyrosine phosphorylation and no interaction with ACK2 [12].
• The interacting ZNF191 protein represents the family of SCAN domain-containing zinc finger proteins, whereas the novel SDP1 protein establishes a new family of genes that encode an isolated SCAN domain [15].

References