Disease relevance of SH3GL2

• Knock-down of endophilin with small interfering RNA (siRNA) had no effect on virion production, but overexpression of endophilin and, to a lesser extent, of several fragments of the protein, result in inhibition of Mo-MuLV virion production, but not of HIV virion production [1].
• The findings imply that endophilin is another component of the large complex that is hijacked by retroviruses to promote virion production [1].
• RESULTS: A search for novel partners interacting with the Gag protein of the Moloney murine leukemia virus (Mo-MuLV) via the yeast two-hybrid protein-protein interaction assay resulted in the identification of endophilin 2, a component of the machinery involved in clathrin-mediated endocytosis [1].
• Endophilin I expression is increased in Alzheimer's disease patients [2]

High impact information on SH3GL2

• We report here a direct interaction between voltage-gated Ca2+ channels and endophilin, a key regulator of clathrin-mediated synaptic vesicle endocytosis [3].
• Introduction into hippocampal neurons of a dominant-negative endophilin construct, which constitutively binds to Ca2+ channels, significantly reduces endocytosis-mediated uptake of FM 4-64 dye without abolishing exocytosis [3].
• Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors [4].
• Here we show that endophilin I is essential for the formation of synaptic-like microvesicles (SLMVs) from the plasma membrane [5].
• Here, we demonstrate that Arc/Arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis [6].

Biological context of SH3GL2

• Endophilin dimerises through its N-terminus, and participates at multiple stages in clathrin-coated endocytosis, from early membrane invagination to synaptic vesicle uncoating [7].
• Therefore, endophilin-1 may serve to couple vesicle biogenesis with intracellular signalling cascades [7].
• The dramatic effects of the SH3 domain of endophilin led us to propose a model for the temporal order of addition of endophilin and its binding partner synaptojanin in the coated vesicle cycle [8].
• SH3GL2, which was one of the 15 special genes, was located at one of the special chromosome regions, 9p12-pter [9].
• This interaction served as an autophosphorylation-dependent scaffold to allow Src phosphorylation of endophilin A2 at Tyr315 [10].

Anatomical context of SH3GL2

• Generation of high curvature membranes mediated by direct endophilin bilayer interactions [11].
• Endophilin B, a protein with homology to endophilin 1, partially localizes to the Golgi complex and also deforms lipid bilayers into tubules, underscoring a potential role of endophilin family members in diverse tubulovesicular membrane-trafficking events in the cell [11].
• In the brain, EEN-B1 and EEN-B2 mRNA are preferentially expressed in the cerebellar Purkinje and granule cells, dentate gyrus cells, hippocampal pyramidal neurons and cerebral granule cells [12].
• Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase [13].
• Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin [14].

Associations of SH3GL2 with chemical compounds

• The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity [15].
• These include the GTPase dynamin, the lysophosphatidic acid acyl transferase endophilin, and the phosphoinositide phosphatase synaptojanin [16].
• Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid [5].
• Interestingly, itch co-localizes with markers of the endosomal system in a C2 domain-dependent manner and upon EGF stimulation, endophilin A1 translocates to an EGF-positive endosomal compartment where it colocalizes with itch [17].
• These results support the hypothesis that a conversion of lysophosphatidic acid into phosphatidic acid by endophilin or BARS (50 kDa brefeldin A ribosylated substrate) may induce negative spontaneous monolayer curvature and regulate endocytic and Golgi membrane fission [18].

Physical interactions of SH3GL2

• Dynamin interacts with a number of partners such as endophilin and proteins involved in coordination of endocytosis with motor molecules [19].

Co-localisations of SH3GL2

• 3. We also show that endophilin 1 and endophilin 3 co-localize with VGLUT1 in synaptic terminals of differentiated rat neocortical neurons in primary culture [20].

Other interactions of SH3GL2

• In addition to synaptic vesicle formation, endophilin-1 complexes with signalling molecules, including cell surface receptors, metalloprotease disintegrins and germinal centre kinase-like kinase (GLK) [7].
• They also recruit CIN85-endophilin in the complex with activated receptors, thus controlling receptor endocytosis [21].
• By using mAb 806, which recognizes an EGFR-activation state and preferentially immunoprecipitates DeltaEGFR, we show that DeltaEGFR did not interact with Cbls, SETA, or endophilin A1, providing a mechanistic explanation for its lack of internalization [22].
• EEN is a member of the endocytic endophilin family but its function in regulating endocytosis remains unclear [23].
• In this issue of Neuron, Schuske et al. and Verstreken et al. show that the lipid-modifying enzyme endophilin recruits and stabilizes the polyphosphoinositide phosphatase synaptojanin at nerve terminals [24].

Analytical, diagnostic and therapeutic context of SH3GL2

• METHOD: Real-time PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein expression and find the various rules of SH3GL2 gene in LSCC [25].
• To further explore its roles in intracellular signaling, we employed protein precipitations and matrix-assisted laser desorption/ionization mass-spectrometry and identified EEN/endophilin II as a novel partner of BPGAP1 [23].
• Endophilin is enriched in the brain, and immunofluorescence analysis reveals a high concentration of the protein in synaptic terminals, where it colocalizes with synaptojanin [26].
• Titration experiments suggest that the binding sites for inclusion of endophilin into viral particles are limited and saturable [1].

References