Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions.
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.
Kurshan
Peri T
PT
F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Massachusetts, USA.
Oztan
Asli
A
Schwarz
Thomas L
TL
D000818:Animals; D030801:Animals, Genetically Modified; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D016253:Microscopy, Immunoelectron / Q000379:methods; D009154:Mutation / Q000502:physiology; D009469:Neuromuscular Junction / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000502:physiology* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology
C498993:Ank2 protein, Drosophila; D017487:Ankyrins; D015220:Calcium Channels; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases