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 release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an a...
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2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55382-9 |
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| author | J. Lützkendorf T. Matkovic-Rachid S. Liu T. Götz L. Gao O. Turrel M. Maglione M. Grieger S. Putignano N. Ramesh T. Ghelani A. Neumann N. Gimber J. Schmoranzer A. Stawrakakis B. Brence D. Baum Kai Ludwig M. Heine T. Mielke F. Liu A. M. Walter M. C. Wahl S. J. Sigrist |
| author_facet | J. Lützkendorf T. Matkovic-Rachid S. Liu T. Götz L. Gao O. Turrel M. Maglione M. Grieger S. Putignano N. Ramesh T. Ghelani A. Neumann N. Gimber J. Schmoranzer A. Stawrakakis B. Brence D. Baum Kai Ludwig M. Heine T. Mielke F. Liu A. M. Walter M. C. Wahl S. J. Sigrist |
| author_sort | J. Lützkendorf |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-608b6cdea2fc4f9f84621c324d498127 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-608b6cdea2fc4f9f84621c324d4981272025-01-05T12:40:52ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55382-9Blobby is a synaptic active zone assembly protein required for memory in DrosophilaJ. Lützkendorf0T. Matkovic-Rachid1S. Liu2T. Götz3L. Gao4O. Turrel5M. Maglione6M. Grieger7S. Putignano8N. Ramesh9T. Ghelani10A. Neumann11N. Gimber12J. Schmoranzer13A. Stawrakakis14B. Brence15D. Baum16Kai Ludwig17M. Heine18T. Mielke19F. Liu20A. M. Walter21M. C. Wahl22S. J. Sigrist23Freie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute of Chemistry and Biochemistry/Structural BiochemistryFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsFreie Universität Berlin, Institute for Biology and GeneticsCharité- Universitätsmedizin, Advanced Medical Bioimaging Core FacilityCharité- Universitätsmedizin, Advanced Medical Bioimaging Core FacilityFreie Universität Berlin, Institute for Biology and GeneticsZuse Institute Berlin, Department of Visual and Data-Centric ComputingZuse Institute Berlin, Department of Visual and Data-Centric ComputingFreie Universität Berlin, Institut für Chemie and Biochemie, Forschungszentrum für ElektronenmikroskopieInstitute of Developmental Biology and Neurobiology, Johannes Gutenberg University MainzMax Planck Institute for Molecular Genetics, Berlin, Microscopy and Cryo-Electron Microscopy Service GroupLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-BuchLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-BuchFreie Universität Berlin, Institute of Chemistry and Biochemistry/Structural BiochemistryFreie Universität Berlin, Institute for Biology and GeneticsAbstract 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.https://doi.org/10.1038/s41467-024-55382-9 |
| spellingShingle | J. Lützkendorf T. Matkovic-Rachid S. Liu T. Götz L. Gao O. Turrel M. Maglione M. Grieger S. Putignano N. Ramesh T. Ghelani A. Neumann N. Gimber J. Schmoranzer A. Stawrakakis B. Brence D. Baum Kai Ludwig M. Heine T. Mielke F. Liu A. M. Walter M. C. Wahl S. J. Sigrist Blobby is a synaptic active zone assembly protein required for memory in Drosophila Nature Communications |
| title | Blobby is a synaptic active zone assembly protein required for memory in Drosophila |
| title_full | Blobby is a synaptic active zone assembly protein required for memory in Drosophila |
| title_fullStr | Blobby is a synaptic active zone assembly protein required for memory in Drosophila |
| title_full_unstemmed | Blobby is a synaptic active zone assembly protein required for memory in Drosophila |
| title_short | Blobby is a synaptic active zone assembly protein required for memory in Drosophila |
| title_sort | blobby is a synaptic active zone assembly protein required for memory in drosophila |
| url | https://doi.org/10.1038/s41467-024-55382-9 |
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