829C Poster - 13. Neural development and physiology
Saturday April 09, 1:30 PM - 3:30 PM

Investigating roles of conserved domains in the calcium channel subunit α2δ-3 during synapse development


Authors:
Marina Bostelman; Heather Broihier

Affiliation: Case Western Reserve University, Cleveland, OH

Keywords:
f. neuromuscular junction; c. TGFbeta

Synapses are highly specialized for neurotransmitter signaling, yet activity-dependent growth factor release also plays critical roles at synapses. While efficient neurotransmitter signaling relies on precise apposition of release sites and neurotransmitter receptors, molecular mechanisms enabling high-fidelity growth factor signaling within the synaptic micro- environment remain obscure. At the Drosophila neuromuscular junction (NMJ), the highly evolutionarily conserved auxiliary calcium channel subunit α2δ-3 promotes an activity-dependent, autocrine Bone Morphogenic Protein (BMP) signal by functioning as an extracellular scaffold, thereby regulating synapse density, structure, and function. Furthermore, α2δ-3’s promotion of BMP signaling is independent of its canonical role in the localization of the pore-forming α1 calcium channel subunit, Cacophony. How these functions are separated, and what roles several evolutionarily conserved protein domains within α2δ-3’s structure play in each of these functions, is currently unknown. This question is being addressed by utilizing the CRISPR-Cas9 gene editing system to generate Drosophila lines containing deletions or modifications of highly conserved key motifs within α2δ-3. Assessing NMJ morphology and function in these mutants at embryonic and larval stages will provide insight into the role of these motifs in synapse formation throughout early Drosophila development.