ArticlePLoS biology2015
A voltage-gated calcium channel regulates lysosomal fusion with endosomes and autophagosomes and is required for neuronal homeostasis.
Article in PLoS biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Mitochondrial and lysosomal dysfunctions might be involved in the pathogenesis of the CACNA1A-related neurodevelopmental disorders according to in vitro studies.Biological research · 2025Article
- Article
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- Bichromatic Exon-Reporters Reveal Voltage-Gated CaeNeuro · 2025Article
- Enhanced γ-aminobutyric acid levels promote degeneration of silk glands following spermidine supplementation in Bombyx mori.Amino acids · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Regulation of the NLRP3 inflammasome by autophagy and mitophagy.Immunological reviews · 2025Review
- The senescent synapse: A look at autophagy, calcium handling, and mitochondrial bioenergetics at the synapse in ageing and Parkinson's disease.Current research in physiology · 2025Review
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Using team-based precision medicine to advance understanding of rare genetic brain disorders.Journal of neurodevelopmental disorders · 2024Review
- Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's.The European journal of neuroscience · 2024Article
- Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer's disease and beyond.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Article
- Lysosomal Potassium Channels.Handbook of experimental pharmacology · 2023Review
- Fluorescent indicators for imaging membrane potential of organelles.Current opinion in chemical biology · 2022Review
- Depleted Calcium Stores and Increased Calcium Entry in Rod Photoreceptors of theInternational journal of molecular sciences · 2022Article
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- The Alzheimer's gene SORL1 is a regulator of endosomal traffic and recycling in human neurons.Cellular and molecular life sciences : CMLS · 2022Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Autophagy helps deliver sequestered intracellular cargo to lysosomes for proteolytic degradation and thereby maintains cellular homeostasis by preventing accumulation of toxic substances in cells. In a forward mosaic screen in Drosophila designed to identify genes required for neuronal function and maintenance, we identified multiple cacophony (cac) mutant alleles. They exhibit an age-dependent accumulation of autophagic vacuoles (AVs) in photoreceptor terminals and eventually a degeneration of the terminals and surrounding glia. cac encodes an α1 subunit of a Drosophila voltage-gated calcium channel (VGCC) that is required for synaptic vesicle fusion with the plasma membrane and neurotransmitter release. Here, we show that cac mutant photoreceptor terminals accumulate AV-lysosomal fusion intermediates, suggesting that Cac is necessary for the fusion of AVs with lysosomes, a poorly defined process. Loss of another subunit of the VGCC, α2δ or straightjacket (stj), causes phenotypes very similar to those caused by the loss of cac, indicating that the VGCC is required for AV-lysosomal fusion. The role of VGCC in AV-lysosomal fusion is evolutionarily conserved, as the loss of the mouse homologues, Cacna1a and Cacna2d2, also leads to autophagic defects in mice. Moreover, we find that CACNA1A is localized to the lysosomes and that loss of lysosomal Cacna1a in cerebellar cultured neurons leads to a failure of lysosomes to fuse with endosomes and autophagosomes. Finally, we show that the lysosomal CACNA1A but not the plasma-membrane resident CACNA1A is required for lysosomal fusion. In summary, we present a model in which the VGCC plays a role in autophagy by regulating the fusion of AVs with lysosomes through its calcium channel activity and hence functions in maintaining neuronal homeostasis.
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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.