ArticleThe Journal of cell biology2021
ALS2 regulates endosomal trafficking, postsynaptic development, and neuronal survival.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Single-cell profiling identifies hair cell SLC35F1 deficiency as a signature of primate cochlear aging.Nature aging · 2025Article
- Genetic, developmental, and neural changes underlying the evolution of butterfly mate preference.PLoS biology · 2025Article
- Review
- Vav independently regulates synaptic growth and plasticity through distinct actin-based processes.The Journal of cell biology · 2022Article
- γ-secretase promotes Drosophila postsynaptic development through the cleavage of a Wnt receptor.Developmental cell · 2022Article
- RNA-binding FMRP and Staufen sequentially regulate the Coracle scaffold to control synaptic glutamate receptor and bouton development.Development (Cambridge, England) · 2022Article
- Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the human ALS2 gene cause recessive juvenile-onset amyotrophic lateral sclerosis and related motor neuron diseases. Although the ALS2 protein has been identified as a guanine-nucleotide exchange factor for the small GTPase Rab5, its physiological roles remain largely unknown. Here, we demonstrate that the Drosophila homologue of ALS2 (dALS2) promotes postsynaptic development by activating the Frizzled nuclear import (FNI) pathway. dALS2 loss causes structural defects in the postsynaptic subsynaptic reticulum (SSR), recapitulating the phenotypes observed in FNI pathway mutants. Consistently, these developmental phenotypes are rescued by postsynaptic expression of the signaling-competent C-terminal fragment of Drosophila Frizzled-2 (dFz2). We further demonstrate that dALS2 directs early to late endosome trafficking and that the dFz2 C terminus is cleaved in late endosomes. Finally, dALS2 loss causes age-dependent progressive defects resembling ALS, including locomotor impairment and brain neurodegeneration, independently of the FNI pathway. These findings establish novel regulatory roles for dALS2 in endosomal trafficking, synaptic development, and neuronal survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.