PMID- 10024875
OWN - NLM
STAT- MEDLINE
DCOM- 19990312
LR  - 20190915
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 3
IP  - 1
DP  - 1999 Jan
TI  - Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to
      mutations in the beta 3A subunit of the AP-3 adaptor.
PG  - 11-21
AB  - Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defective 
      lysosome-related organelles. Here, we report the identification of two HPS
      patients with mutations in the beta 3A subunit of the heterotetrameric AP-3
      complex. The patients' fibroblasts exhibit drastically reduced levels of AP-3 due
      to enhanced degradation of mutant beta 3A. The AP-3 deficiency results in
      increased surface expression of the lysosomal membrane proteins CD63, lamp-1, and
      lamp-2, but not of nonlysosomal proteins. These differential effects are
      consistent with the preferential interaction of the AP-3 mu 3A subunit with
      tyrosine-based signals involved in lysosomal targeting. Our results suggest that 
      AP-3 functions in protein sorting to lysosomes and provide an example of a human 
      disease in which altered trafficking of integral membrane proteins is due to
      mutations in a component of the sorting machinery.
FAU - Dell'Angelica, E C
AU  - Dell'Angelica EC
AD  - Cell Biology and Metabolism Branch, National Institute of Child Health and Human 
      Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Shotelersuk, V
AU  - Shotelersuk V
FAU - Aguilar, R C
AU  - Aguilar RC
FAU - Gahl, W A
AU  - Gahl WA
FAU - Bonifacino, J S
AU  - Bonifacino JS
LA  - eng
SI  - GENBANK/AF092092
PT  - Journal Article
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Antigens, CD)
RN  - 0 (CD63 protein, human)
RN  - 0 (HPS1 protein, human)
RN  - 0 (Lysosome-Associated Membrane Glycoproteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Monomeric Clathrin Assembly Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Platelet Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tetraspanin 30)
RN  - 0 (clathrin assembly protein AP180)
RN  - 0 (lysosomal proteins)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport
MH  - Albinism, Oculocutaneous/*genetics
MH  - Antigens, CD/metabolism
MH  - DNA Mutational Analysis
MH  - Fibroblasts
MH  - Flow Cytometry
MH  - Humans
MH  - Lysosome-Associated Membrane Glycoproteins
MH  - Melanosomes/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Microscopy, Fluorescence
MH  - Molecular Sequence Data
MH  - *Monomeric Clathrin Assembly Proteins
MH  - Nerve Tissue Proteins/*genetics
MH  - Phosphoproteins/*genetics
MH  - Platelet Membrane Glycoproteins/metabolism
MH  - Protein Processing, Post-Translational/genetics
MH  - Proteins/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Tetraspanin 30
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - S1097-2765(00)80170-7 [pii]
AID - 10.1016/s1097-2765(00)80170-7 [doi]
PST - ppublish
SO  - Mol Cell. 1999 Jan;3(1):11-21. doi: 10.1016/s1097-2765(00)80170-7.