title: Abnormal expression and subcellular distribution of subunit proteins of the AP-3 adaptor complex lead to platelet storage pool deficiency in the pearl mouse.
abstract: The pearl mouse is a model for Hermansky Pudlak Syndrome (HPS), whose symptoms include hypopigmentation, lysosomal abnormalities, and prolonged bleeding due to platelet storage pool deficiency (SPD). The gene for pearl has recently been identified as the beta3A subunit of the AP-3 adaptor complex. The objective of these experiments was to determine if the expression and subcellular distribution of the AP-3 complex were altered in pearl platelets and other tissues. The beta3A subunit was undetectable in all pearl cells and tissues. Also, expression of other subunit proteins of the AP-3 complex was decreased. The subcellular distribution of the remaining AP-3 subunits in platelets, macrophages, and a melanocyte-derived cell line of pearl mice was changed from the normal punctate, probably endosomal, pattern to a diffuse cytoplasmic pattern. Ultrastructural abnormalities in mutant lysosomes were likewise apparent in mutant kidney and a cultured mutant cell line. Genetically distinct mouse HPS models had normal expression of AP-3 subunits. These and related experiments strongly suggest that the AP-3 complex regulates the biogenesis/function of organelles of platelets and other cells and that abrogation of expression of the AP-3 complex leads to platelet SPD.
authors.affiliation: Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhen
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: N A
authors.initials: NA
authors.lastname: Bright
authors.forename: A A
authors.initials: AA
authors.lastname: Peden
authors.forename: A B
authors.initials: AB
authors.lastname: Seymour
authors.forename: E K
authors.initials: EK
authors.lastname: Novak
authors.forename: R
authors.initials: R
authors.lastname: Elliott
authors.forename: M B
authors.initials: MB
authors.lastname: Gorin
authors.forename: M S
authors.initials: MS
authors.lastname: Robinson
authors.forename: R T
authors.initials: RT
authors.lastname: Swank
mesh_terms: D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D016115:Albinism, Oculocutaneous / Q000097:blood / Q000235:genetics / Q000473:pathology; D000818:Animals; D001692:Biological Transport; D001792:Blood Platelets / Q000502:physiology / Q000648:ultrastructure; D015870:Gene Expression; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D034041:Monomeric Clathrin Assembly Proteins; D009154:Mutation; D010981:Platelet Storage Pool Deficiency / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; C439023:clathrin assembly protein AP180