2024-12-17 ブラウン大学
<関連情報>
- https://www.brown.edu/news/2024-12-17/carney-microscope
- https://www.biorxiv.org/content/10.1101/2023.06.15.544950v1.article-info
- https://elifesciences.org/reviewed-preprints/88412
WFIKKN2は、多様なDCCファミリー受容体を介してシグナルを伝達する、2つの機能を持つ軸索ガイダンスキューである WFIKKN2 is a bifunctional axon guidance cue that signals through divergent DCC family receptors
Kelsey R. Nickerson, Irene Tom, Elena Cortés, Jane R. Abolafia, Engin Özkan, Lino C. Gonzalez, Alexander Jaworsk
bioRxiv Posted:June 15, 2023
DOI:https://doi.org/10.1101/2023.06.15.544950
Abstract
Axon pathfinding is controlled by attractive and repulsive molecular cues that activate receptors on the axonal growth cone, but the full repertoire of axon guidance molecules remains unknown. The vertebrate DCC receptor family contains the two closely related members DCC and Neogenin with prominent roles in axon guidance and three additional, divergent members – Punc, Nope, and Protogenin – for which functions in neural circuit formation have remained elusive. We identified a secreted Punc/Nope/Protogenin ligand, WFIKKN2, which guides mouse peripheral sensory axons through Nope-mediated repulsion. In contrast, WFIKKN2 attracts motor axons, but not via Nope. These findings identify WFIKKN2 as a bifunctional axon guidance cue that acts through divergent DCC family members, revealing a remarkable diversity of ligand interactions for this receptor family in nervous system wiring.
シナプスの機能的多様性を形成するCa2+チャネルと活性帯タンパク質の量は、入力特異的シナプス組織と交差する Ca2+ channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity
Audrey T Medeiros,Scott J Gratzauthor,Ambar Delgado,Jason T Ritt,Kate M OConnor-Giles
eLife Reviewed Preprint
v2:July 18, 2024
DOI:https://doi.org/10.7554/eLife.88412.2
Abstract
Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it is thus critical to determine the factors that contribute to the functional diversity of synapses. We investigated the contributions of voltage-gated calcium channel (VGCC) abundance, spatial organization, and subunit composition to synapse diversity among and between synapses formed by two closely related Drosophila glutamatergic motor neurons with distinct neurotransmitter release probabilities (Pr). Surprisingly, VGCC levels are highly predictive of heterogeneous Pr among individual synapses of either low- or high-Pr inputs, but not between inputs. We find that the same number of VGCCs are more densely organized at high-Pr synapses, consistent with tighter VGCC-synaptic vesicle coupling. We generated endogenously tagged lines to investigate VGCC subunits in vivo and found that the α2δ-3 subunit Straightjacket along with the CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators of VGCCs, are less abundant at high-Pr inputs, yet positively correlate with Pr among synapses formed by either input. Consistently, both Straightjacket and Bruchpilot levels are dynamically increased across AZs of both inputs when neurotransmitter release is potentiated to maintain stable communication following glutamate receptor inhibition. Together, these findings suggest a model in which VGCC and AZ protein abundance intersects with input-specific spatial and molecular organization to shape the functional diversity of synapses.
