Annotated protein:	AP-3 complex subunit delta-1 (AP-3 complex subunit delta) (Adaptor-related protein complex 3 subunit delta-1) (Delta-adaptin) (mBLVR1). Gene symbol: AP3D1. Taxonomy: Mus musculus (Mouse). Uniprot ID: O54774
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SynGO gene info:	SynGO data @ AP3D1
Ontology domain:	Biological Process
SynGO term:	synaptic vesicle budding from endosome (GO:0016182)
Synapse type(s):	brain
Annotated paper:	Blumstein J, et al. "The neuronal form of adaptor protein-3 is required for synaptic vesicle formation from endosomes" J Neurosci. 2001 Oct 15;21(20):8034-42 PMID:11588176
Figure(s):	Fig.1, Fig.6
Annotation description:	The authors have developed an assay that examines the formation of synaptic like microvesicles from endosomes isolated from PC12 cells. The synaptic vesicle nature of the vesicles is indicated by the fact they sort the synaptic vesicle protein VAMP. The budding of these VAMP positive vesicles is supported by cytosol from wild type mice but is not supported by cytosol from Mocha mice. Mocha mice have a spontaneous mutation in AP-3 delta that renders AP-3 delta null and leads to loss AP-3 complexes. 15/8/2017 Pim - Literal: "Mocha brain cytosol, **which lacks all AP-3**, cannot provide coat to these vesicles ..." (emphasis added) - Fig.6 shows partial co-localization of AP-3 delta with neuronal AP-3 complex --+ Breakdown of paper by Pim --++ Introduction Ubiquitous AP-3 subunits: delta-adaptin --> AP3D1 beta3A-adaptin --> AP3B1 mu3A-adaptin --> AP3M1 sigma3A or sigma3B-adaptin (?) --> AP3S1 or AP3S2 Neuronal AP-3 subunits: beta3B-adaptin --> AP3B2 mu3B-adaptin --> AP3M2 The adaptin beta, mu and sigma subunits in the AP3 complex are variable. Neurons may use neuron specific variants of beta and/or mu subunits. The AP-3 complex is referred to as the 'neuronal AP-3' complex. -++ Results The paper tries to study the involvement of neuron specific AP-3 complexes in SV budding. The role of the beta3B-adaptin and Mu3B-adaptin are assessed in a in vitro budding assay using: - beta3B-adaptin immunodepleted cytosol - Cytosol from Mocha mouse brain that lacks neuronal AP3 proteins Mu3B-adaptin resulting in a removal of all AP-3 complex proteins neuronal+ubiquitous Fig.1: removal of removal of all AP-3 complex proteins (mocha mouse; neuronal+ubiquitous) reduces SV budding with 50%. Immuno-depletion of neuronal+ubiquitous AP-3 from this assay (neuronal+unibuitous) shows the same 50% reduction. Fig.3: removal of neuronal AP-3 complexes (beta3B-adaptin immunodepleted cytosol) reduces SV budding with 50%. These data strongly suggest that synaptic vesicle budding from endosomes is attributable solely to the neuronal form of the AP-3 complex. Fig.4: the neuronal AP-3 is not the major form of AP-3 in brain. Conclusions: - The neuronal AP-3 complex that contains beta3B-adaptin is shown to be involved in SV budding from endosomes. - Based on these experiments it is unclear whether the beta3B-adaptin-containing neuronal AP-3 complex also contains the mu3B-adaptin subunit. The mu3B-adaptin KO is used as an apporach that removes all AP-3 subunits. -++ Possible annotations: - DIRECT: beta3B-adaptin --> SV budding from endosome - INFERRED: delta-adaptin --> SV budding from endosome (based on fixed participation in AP-3 complexes) Problematic annotations: - sigma3A/sigma3B-adaptin: the experimental show effect of 'sigma3' depletion on SV budding, but do not distinguish between sigma3A/sigma3B-adaptin genes (literal: "pan-ς3 antibodies were prepared against GST fusion protein composed of residues 16-180 of ς3B") - mu3A/mu3B-adaptin: experiments do not show role of mu3A-adaptin and/or mu3B-adaptin in SV budding.
Evidence tracking, Biological System:	Non-neuronal tissue Cell-free system
Evidence tracking, Protein Targeting:	Genetic transformation (eg; knockout, knockin, mutations) Antibody (detection)
Evidence tracking, Experiment Assay:	radioisotope assay evidence
Annotator(s):	Peter McPherson (ORCID:0000-0001-7806-5662)
Lab:	Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada
Additional literature:	In figure 6 the authors examine synaptic vesicle formation in rat calyx of Held. The SVs are labelled with HRP indicating that they are of endocytic origin. Treatment with brefeldin A, which disrupts AP-3 function decreases the number of HRP-labeled SVs. @ PMID:22974146 The authors used hippocampal slices from control mice and AP-3 beta KO mice. They compared the frequency of asynchronously released synaptic events between wild-type (WT) and AP-3b2 KO animals in response to short stimulus trains (10 evoked EPSCs (eEPSCs) at 20 Hz) (Fig. 4a). The frequency of EPSCs measured in the 500 ms time-window 200 ms after the last stimulus was almost twofold lower in AP-3b2 KOs (4.4±0.3 Hz versus 7.8±0.6 Hz; (Fig. 4c). @ PMID:25410111
SynGO annotation ID:	1282
Dataset release (version):	20231201
View annotation as GO-CAM model: