High impact information on endoA

• Here we have characterized the endocytosis that persists in null alleles of Drosophila synaptojanin and endophilin [1].
• Analyses of quantal size, FM1-43 loading, and dynamin function further demonstrate that, even in the absence of synaptojanin or endophilin, vesicles undergo full fusion and re-formation [1].
• Endophilin is required presynaptically at the neuromuscular junction, and absence of Endophilin dramatically impairs endocytosis in vivo [2].
• Mutant larvae that lack Endophilin fail to take up FM1-43 dye in synaptic boutons, indicating an inability to retrieve synaptic membrane [2].
• The protraction was more pronounced in evoked and spontaneous quantal EPSCs than in action potential-evoked multiquantal EPSCs; reduced in quantal EPSCs from endophilin null mutants, which maintain release via kiss-and-run; and dependent on synaptotagmin isoform, calcium, and protein phosphorylation [3].

Biological context of endoA

• Endophilin promotes a late step in endocytosis at glial invaginations in Drosophila photoreceptor terminals [4].
• Studies in cell-free systems and the lamprey giant synapse have implicated crucial roles for amphiphysin and endophilin in synaptic transmission [5].
• This mutant phenotype can be restored to wild-type by complementation with a functional copy of the des gene (Endo, K., Akiyama, T., Kobayashi S., and Okada, M. (1996) Mol. Gen. Genet. 253, 157-165) [6].

Anatomical context of endoA

• Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating [7].
• Moreover, synj; endo double mutant synaptic terminals exhibit properties that are very similar to terminals of each single mutant, and overexpression of Endophilin can partially rescue the functional defects in partial loss-of-function synj mutants [7].
• Detailed ultrastructural analysis of endo null mutant photoreceptor synapses fails to reveal a defect at early stages of vesicle reformation but, instead, reveals an accumulation of clusters of electron-dense, apparently nonfunctional, late endocytotic vesicles [4].
• Decreased endophilin activity results in alterations in the neuromuscular junction structure and physiology [5].

Associations of endoA with chemical compounds

• Like its mammalian homologue, D-endoA exhibits lysophosphatidic acid acyl transferase activity and contains a functional SH3 domain [8].

Other interactions of endoA

• Immunofluorescence studies show colocalization of endophilin with dynamin consistent with a possible role in synaptic vesicle recycling [5].

Analytical, diagnostic and therapeutic context of endoA

• Mutants with reduced D-endoA levels exhibit a range of defects of synaptic vesicle endocytosis, as observed at L3 larvae NMJs using FM1-43 uptake and electron microscopy [8].

References