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Hermansky-Pudlak protein complexes, AP-3 and BLOC-1, differentially regulate presynaptic composition in the striatum and hippocampus.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2010 Jan 20; Vol. 30 (3), pp. 820-31. - Publication Year :
- 2010
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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.
- Subjects :
- Adaptor Protein Complex 3
Adaptor Protein Complex beta Subunits
Animals
Corpus Striatum metabolism
Embryo, Mammalian
Gene Expression Regulation genetics
Hippocampus metabolism
Intracellular Signaling Peptides and Proteins
Lectins deficiency
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Immunoelectron methods
Neurons cytology
Neurons metabolism
Presynaptic Terminals ultrastructure
R-SNARE Proteins metabolism
Rats
Rats, Sprague-Dawley
Synaptic Vesicles ultrastructure
Synaptophysin metabolism
Synaptosomes metabolism
Synaptosomes ultrastructure
Transcription Factors deficiency
Carrier Proteins metabolism
Corpus Striatum cytology
Hippocampus cytology
Lectins metabolism
Presynaptic Terminals metabolism
Synaptic Vesicles metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 30
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 20089890
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.3400-09.2010