BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes.
The adaptor protein (AP)-3 complex is a component of the cellular machinery that controls protein sorting from endosomes to lysosomes and specialized related organelles such as melanosomes. Mutations in an AP-3 subunit underlie a form of Hermansky-Pudlak syndrome (HPS), a disorder characterized by abnormalities in lysosome-related organelles. HPS in humans can also be caused by mutations in genes encoding subunits of three complexes of unclear function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2, and -3. Here, we report that BLOC-1 interacts physically and functionally with AP-3 to facilitate the trafficking of a known AP-3 cargo, CD63, and of tyrosinase-related protein 1 (Tyrp1), a melanosomal membrane protein previously thought to traffic only independently of AP-3. BLOC-1 also interacts with BLOC-2 to facilitate Tyrp1 trafficking by a mechanism apparently independent of AP-3 function. Both BLOC-1 and -2 localize mainly to early endosome-associated tubules as determined by immunoelectron microscopy. These findings support the idea that BLOC-1 and -2 represent hitherto unknown components of the endosomal protein trafficking machinery.
Di Pietro
Santiago M
SM
Department of Human Genetics, University of California, Los Angeles, CA 90095, USA.
Falcón-Pérez
Juan M
JM
Tenza
Danièle
D
Setty
Subba R G
SR
Marks
Michael S
MS
Raposo
Graça
G
Dell'Angelica
Esteban C
EC
D033963:Adaptor Protein Complex 3 / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008544:Melanocytes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D060149:Tetraspanin 30
D033963:Adaptor Protein Complex 3; D015703:Antigens, CD; C554586:CD63 protein, human; D002352:Carrier Proteins; C554587:Cd63 protein, mouse; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D010980:Platelet Membrane Glycoproteins; D021122:Protein Subunits; D060149:Tetraspanin 30; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse