Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching.
Cell
; 187(18): 5081-5101.e19, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-38996528
ABSTRACT
In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.
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Base de dados:
MEDLINE
Assunto principal:
Axônios
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Sinapses
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Transdução de Sinais
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Neurônios Receptores Olfatórios
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Proteínas de Drosophila
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Drosophila melanogaster
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article