Robo2 regulates synaptic oxytocin content by affecting actin dynamics
- Anbalagan, S., Blechman, J., Gliksberg, M., Gordon, L., Rotkopf, R., Dadosh, T., Shimoni, E., Levkowitz, G.
- eLIFE 8: (Journal)
- Registered Authors
- Anbalagan, Savani, Blechman, Janna, Gliksberg, Michael, Levkowitz, Gil
- developmental biology, neuroscience, zebrafish
- MeSH Terms
- Animals, Genetically Modified
- Fluorescence Recovery After Photobleaching
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Microscopy, Fluorescence, Multiphoton
- Receptors, Immunologic/genetics*
- Receptors, Immunologic/metabolism
- Signal Transduction/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- cdc42 GTP-Binding Protein/genetics
- cdc42 GTP-Binding Protein/metabolism
- 31180321 Full text @ Elife
Anbalagan, S., Blechman, J., Gliksberg, M., Gordon, L., Rotkopf, R., Dadosh, T., Shimoni, E., Levkowitz, G. (2019) Robo2 regulates synaptic oxytocin content by affecting actin dynamics. eLIFE. 8.
The regulation of neuropeptide level at the site of release is essential for proper neurophysiological functions. We focused on a prominent neuropeptide, oxytocin (OXT) in the zebrafish as an in vivo model to visualize and quantify OXT content at the resolution of a single synapse. We found that OXT-loaded synapses were enriched with polymerized actin. Perturbation of actin filaments by either cytochalasin-D or conditional Cofilin expression resulted in decreased synaptic OXT levels. Genetic loss of robo2 or slit3 displayed decreased synaptic OXT content and robo2 mutants displayed reduced mobility of the actin probe Lifeact-EGFP in OXT synapses.Using a novel transgenic reporter allowing real-time monitoring of OXT-loaded vesicles, we showed that robo2 mutants display slower rate of vesicles accumulation. OXT-specific expression of dominant-negative Cdc42, which is a key regulator of actin dynamics and a downstream effector of Robo2, led to a dose-dependent increase in OXT content in WT, and a dampened effect in robo2 mutants. Our results link Slit3-Robo2-Cdc42, which controls local actin dynamics, with the maintenance of synaptic neuropeptide levels.
Errata / NotesThis article is corrected by ZDB-PUB-220906-219 .
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes