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Blobby is a synaptic active zone assembly protein required for memory in Drosophila

ABSTRACT: At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle (SV) release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify a novel Drosophila AZ protein, "Blobby", essential for proper AZ nano-organization. Blobby biochemically associates with the ELKS family AZ scaffold protein Bruchpilot (BRP) and integrates into newly forming AZs. Loss of Blobby results in fewer AZs forming, ectopic AZ scaffold protein accumulations ("blobs") and disrupts nanoscale architecture of the BRP-AZ scaffold. Functionally, blobby mutants show diminished evoked synaptic currents due to reduced SV release probability and fewer functional SV release sites. Blobby is also present in adult brain synapses, and post-developmental knockdown of Blobby in the mushroom body impairs olfactory aversive memory consolidation. Thus, our analysis identifies a new layer of AZ regulation critical for developmental AZ assembly but also for AZ-mediated plasticity controlling behavior.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Brain

SUBMITTER: Max Ruwolt

LAB HEAD: Stephan Sigrist

PROVIDER: PXD058345 | Pride | 2025-03-17

REPOSITORIES: Pride

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			Action	DRS
	HS1031_perseus.txt	Txt
	L1_20190903_HS_1031_FL_BRP_1_1.raw	Raw
	L1_20190903_HS_1031_FL_BRP_1_2.raw	Raw
	L1_20190903_HS_1031_FL_BRP_1_3.raw	Raw
	L1_20190903_HS_1031_FL_BRP_2_1.raw	Raw

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