Endocytosis restricts synapse growth by attenuating Highwire/PHR1-dependent JNK signaling in a pathway parallel to the BMP signaling DOI Open Access

Srikanth Pippadpally,

Saumitra Dey Choudhury,

Anjali Bisht

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Endocytosis regulates the retrieval of synaptic membranes and trafficking growth signaling receptors. While Drosophila endocytic mutants show overgrowth at neuromuscular junctions (NMJs), pathways by which endocytosis restricts synapse remain poorly understood. Here, we demonstrate that σ2-adaptin, one obligate subunits AP2 complex, facilitates degradation E3-ubiquitin ligase Highwire (Hiw)/PHR1 inhibits c-Jun N-terminal kinase (JNK) signaling. This function σ2-adaptin is independent its Bone Morphogenetic Protein (BMP) regulation. Loss leads to Hiw accumulation mislocalization in neuronal cell body, leading elevated MAP3K Wallenda levels. Stabilizing expressing Rae1 or genetically blocking JNK suppresses defects observed mutants. Remarkably, BMP suppressed mutant wild-type Finally, loss Rab11 but not Rab5 Rab7 accumulation/mislocalization body akin We propose a model Rab11-mediated attenuates pathway parallel restrict growth.

Language: Английский

Endocytosis restricts synapse growth by attenuating Highwire/PHR1-dependent JNK signaling in a pathway parallel to the BMP signaling DOI Open Access

Srikanth Pippadpally,

Saumitra Dey Choudhury,

Anjali Bisht

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Endocytosis regulates the retrieval of synaptic membranes and trafficking growth signaling receptors. While Drosophila endocytic mutants show overgrowth at neuromuscular junctions (NMJs), pathways by which endocytosis restricts synapse remain poorly understood. Here, we demonstrate that σ2-adaptin, one obligate subunits AP2 complex, facilitates degradation E3-ubiquitin ligase Highwire (Hiw)/PHR1 inhibits c-Jun N-terminal kinase (JNK) signaling. This function σ2-adaptin is independent its Bone Morphogenetic Protein (BMP) regulation. Loss leads to Hiw accumulation mislocalization in neuronal cell body, leading elevated MAP3K Wallenda levels. Stabilizing expressing Rae1 or genetically blocking JNK suppresses defects observed mutants. Remarkably, BMP suppressed mutant wild-type Finally, loss Rab11 but not Rab5 Rab7 accumulation/mislocalization body akin We propose a model Rab11-mediated attenuates pathway parallel restrict growth.

Language: Английский

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