ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Hermansky-Pudlak protein complexes, AP-3 and BLOC-1, differentially regulate presynaptic composition in the striatum and hippocampus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
- Synaptic vesicles that store monoamines and glutamate differ in protein composition.Science advances · 2026Article
- BLOC-1 and BORC: Complex regulators of endolysosomal dynamics.Cell chemical biology · 2025Review
- Properties of Hippocampal Mossy Fibre Synapses in VAMP7 KO Mice.The European journal of neuroscience · 2025Article
- Dysbindin-1 Mutation Alters Prefrontal Cortex Extracellular Glutamate and Dopamine In Vivo.International journal of molecular sciences · 2024Article
- Masks of Albinism: Clinical Spectrum of Hermansky-Pudlak Syndrome.International journal of molecular sciences · 2024Article
- Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2.The Journal of biological chemistry · 2024Article
- Adaptor protein-3 produces synaptic vesicles that release phasic dopamine.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Overlapping Machinery in Lysosome-Related Organelle Trafficking: A Lesson from Rare Multisystem Disorders.Cells · 2022Review
- SNX5 targets a monoamine transporter to the TGN for assembly into dense core vesicles by AP-3.The Journal of cell biology · 2022Article
- Effects of the clathrin inhibitor Pitstop-2 on synaptic vesicle recycling at a central synapseFrontiers in synaptic neuroscience · 2022Article
- Hermansky-Pudlak syndrome: Mutation update.Human mutation · 2020Article
- Loss of dysbindin-1 affects GABAergic transmission in the PFC.Psychopharmacology · 2019Article
- The road to lysosome-related organelles: Insights from Hermansky-Pudlak syndrome and other rare diseases.Traffic (Copenhagen, Denmark) · 2019Review
- Synaptic Vesicle Recycling Pathway Determines Neurotransmitter Content and Release Properties.Neuron · 2019Article
- Neurodevelopmental disease mechanisms, primary cilia, and endosomes converge on the BLOC-1 and BORC complexes.Developmental neurobiology · 2018Review
- Sleep/Wake Disruption in a Mouse Model of BLOC-1 Deficiency.Frontiers in neuroscience · 2018Article
- UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes.PLoS genetics · 2017Article
- BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus.Scientific reports · 2017Article
- VGLUT2 Trafficking Is Differentially Regulated by Adaptor Proteins AP-1 and AP-3.Frontiers in cellular neuroscience · 2017Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Endosomal sorting mechanisms mediated by AP-3 and BLOC-1 are perturbed in Hermansky-Pudlak Syndrome, a human genetic condition characterized by albinism and prolonged bleeding (OMIM #203300). Additionally, mouse models defective in either one of these complexes possess defective synaptic vesicle biogenesis (Newell-Litwa et al., 2009). These synaptic vesicle phenotypes were presumed uniform throughout the brain. However, here we report that AP-3 and BLOC-1 differentially regulate the composition of presynaptic terminals in the striatum and dentate gyrus of the hippocampus. Quantitative immunoelectron microscopy demonstrated that the majority of AP-3 immunoreactivity in both wild-type striatum and hippocampus localizes to presynaptic axonal compartments, where it regulates synaptic vesicle size. In the striatum, loss of AP-3 (Ap3d(mh/mh)) resulted in decreased synaptic vesicle size. In contrast, loss of AP-3 in the dentate gyrus increased synaptic vesicle size, thus suggesting anatomically specific AP-3-regulatory mechanisms. Loss-of-function alleles of BLOC-1, Pldn(pa/pa), and Muted(mu/mu) revealed that this complex acts as a brain-region-specific regulator of AP-3. In fact, BLOC-1 deficiencies selectively reduced AP-3 and AP-3 cargo immunoreactivity in presynaptic compartments within the dentate gyrus both at the light and/or electron microscopy level. However, the striatum did not exhibit these BLOC-1-null phenotypes. Our results demonstrate that distinct brain regions differentially regulate AP-3-dependent synaptic vesicle biogenesis. We propose that anatomically restricted mechanisms within the brain diversify the biogenesis and composition of synaptic vesicles.
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