High impact information on Sh3gl2

• Phosphorylation was proposed to regulate the assembly of an endocytic protein complex with amphiphysin or endophilin [1].
• Instead, we found it recruits syndapin I for SVE and does not control amphiphysin or endophilin binding in rat synaptosomes [1].
• We now find that vesicular glutamate transporter VGLUT1 interacts directly with endophilin, a component of the clathrin-dependent endocytic machinery [2].
• Inhibition of the AP3 pathway with brefeldin A rescues the rate of recycling, suggesting a competition between AP2 and -3 pathways, with endophilin recruiting VGLUT1 toward the faster AP2 pathway [2].
• We also show that in a cell-free system, endophilin is not associated with clathrin coats and is a functional partner of dynamin [3].

Biological context of Sh3gl2

• Inhibitory role of endophilin 3 in receptor-mediated endocytosis [4].
• Mutation of serine 1144 to aspartic acid to mimic phosphorylation by Cdk5 inhibited the interaction of synaptojanin 1 with endophilin 1 [5].
• Notably, Cdk5 phosphorylated serine 1144, which is adjacent to the endophilin binding site [5].
• Green fluorescent protein-tagged Src homology 3 (SH3) domains of endophilin I and amphiphysin II, two major binding partners of dynamins, also inhibited AT1A receptor-mediated endocytosis of angiotensin II [6].

Anatomical context of Sh3gl2

• Differential expression of endophilin 1 and 2 dimers at central nervous system synapses [7].
• We show here that antibody-mediated disruption of endophilin function in a tonically stimulated synapse leads to a block in the invagination of clathrin-coated pits adjacent to the active zone and therefore to a block of synaptic vesicle recycling [3].

Associations of Sh3gl2 with chemical compounds

• Endo1 has also been reported to affect endocytosis by converting membrane curvature via its lysophosphatidic acid acyltransferase activity [4].
• We used the divergent C-terminus of VGLUT1 as a bait in a yeast two-hybrid screen to identify and map the interaction between a proline-rich domain of VGLUT1 and the Src homology domain 3 (SH3) domain of endophilin [8].

Other interactions of Sh3gl2

• Preloading of dynamin-1 PRD with the amphiphysin-SH3 domain partially occluded binding of the endophilin-SH3 domain, indicating overlap between the binding sites in the C terminus, but endophilin was still able to interact with the high affinity N-terminal site [9].

Analytical, diagnostic and therapeutic context of Sh3gl2

• Double immunofluorescence in the rat cerebellum shows that most VGLUT1-positive terminals co-express endophilin, whereas VGLUT2-expressing terminals are often devoid of endophilin [8].

References