Mutation in AP-3 delta in the mocha mouse links endosomal transport to storage deficiency in platelets, melanosomes, and synaptic vesicles.
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.
Mental Health Research Institute and Department of Psychiatry, University of Michigan, Ann Arbor 48109, USA.
P
P
Kantheti
X
X
Qiao
M E
ME
Diaz
A A
AA
Peden
G E
GE
Meyer
S L
SL
Carskadon
D
D
Kapfhamer
D
D
Sufalko
M S
MS
Robinson
J L
JL
Noebels
M
M
Burmeister
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D002874:Chromosome Mapping; D011992:Endosomes / Q000378:metabolism*; D015321:Gene Rearrangement; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010981:Platelet Storage Pool Deficiency / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; C113910:Ap3d1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D015032:Zinc