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PMID:19820706

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Citation

Kurshan, PT, Oztan, A and Schwarz, TL (2009) Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions. Nat. Neurosci. 12:1415-23

Abstract

Synaptogenesis involves the transformation of a growth cone into synaptic boutons specialized for transmitter release. In Drosophila embryos lacking the alpha(2)delta-3 subunit of presynaptic, voltage-dependent Ca(2+) channels, we found that motor neuron terminals failed to develop synaptic boutons and cytoskeletal abnormalities arose, including the loss of ankyrin2. Nevertheless, functional presynaptic specializations were present and apposed to clusters of postsynaptic glutamate receptors. The alpha(2)delta-3 protein has been thought to function strictly as an auxiliary subunit of the Ca(2+) channel, but the phenotype of alpha(2)delta-3 (also known as stj) mutations cannot be explained by a channel defect; embryos lacking the pore-forming alpha(1) subunit cacophony formed boutons. The synaptogenic function of alpha(2)delta-3 required only the alpha(2) peptide, whose expression sufficed to rescue bouton formation. Our results indicate that alpha(2)delta proteins have functions that are independent of their roles in the biophysics and localization of Ca(2+) channels and that synaptic architecture depends on these functions.

Links

PubMed PMC2996863 Online version:10.1038/nn.2417

Keywords

Animals; Animals, Genetically Modified; Ankyrins/genetics; Ankyrins/metabolism; Calcium Channels/genetics; Calcium Channels/physiology; Drosophila; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Electric Stimulation/methods; Embryo, Nonmammalian; Gene Expression Regulation, Developmental/genetics; Intracellular Signaling Peptides and Proteins/genetics; Membrane Potentials/genetics; Membrane Potentials/physiology; Microscopy, Immunoelectron/methods; Mutation/physiology; Neuromuscular Junction/cytology; Patch-Clamp Techniques/methods; Presynaptic Terminals/physiology; Presynaptic Terminals/ultrastructure; Protein Subunits/genetics; Protein Subunits/metabolism; Protein-Serine-Threonine Kinases/genetics; Retina/cytology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:A0A0B4K7P4

involved_in

GO:0007528: neuromuscular junction development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4K866

involved_in

GO:0007528: neuromuscular junction development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7K0H4

involved_in

GO:0007528: neuromuscular junction development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q95R75

involved_in

GO:0007528: neuromuscular junction development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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