2025/01/02 by Janine Lützkendorf, Tanja Matkovic-Rachid, Sunbin Liu +21 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Cellular transport and secretion #Genetics, Aging, and Longevity in Model Organisms #Neurobiology and Insect Physiology Research
paper · pdf · doi:10.1038/s41467-024-55382-9
openalex publication_date 2025/01/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional 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 synaptic vesicle release probability and fewer functional 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 an additional layer of AZ regulation critical for developmental AZ assembly but also for AZ-mediated plasticity controlling behavior.