Abstract
The mouse mutant mocha, a model for the Hermansky-Pudlak storage pool deficiency syndrome, is characterized by defective platelets, coat and eye color dilution, lysosomal abnormalities, inner ear degeneration, and neurological deficits. Here, we show that mocha is a null allele of the delta subunit of the adaptor-like protein complex AP-3, which is associated with coated vesicles budding from the trans-Golgi network, and that AP-3 is missing in mocha tissues. In mocha brain, the ZnT-3 transporter is reduced, resulting in a lack of zinc-associated Timm historeactivity in hippocampal mossy fibers. Our results demonstrate that the AP-3 complex is responsible for cargo selection to lysosome-related organelles such as melanosomes and platelet dense granules as well as to neurotransmitter vesicles.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Protein Complex 3
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Adaptor Protein Complex beta Subunits
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Alleles
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Animals
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Base Sequence
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Biological Transport / physiology
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Blood Platelets / metabolism*
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Central Nervous System / metabolism
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Chromosome Mapping
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Endosomes / metabolism*
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Gene Rearrangement
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Melanocytes / metabolism*
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Mutation / genetics*
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Platelet Storage Pool Deficiency / genetics*
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Platelet Storage Pool Deficiency / metabolism
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RNA, Messenger / metabolism
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Synaptic Vesicles / metabolism*
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Transcription Factors / genetics*
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Transcription, Genetic
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Zinc / metabolism
Substances
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Adaptor Protein Complex 3
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Adaptor Protein Complex beta Subunits
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Ap3d1 protein, mouse
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RNA, Messenger
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Transcription Factors
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Zinc