Evidence for distinct membrane traffic pathways to melanosomes and lysosomes in melanocytes.
We report here morphologic and biochemical evidence that melanosomes are distinct from lysosomes. Immunofluorescence analysis revealed that TRP-1, a melanosomal membrane protein, did not colocalize with lysosomal membrane proteins LAMP1 and LGP85 in melan-a cells. Wortmannin treatment of melanocytes enhanced the distinct compartmentalization of these melanosomal/lysosomal membrane proteins by the swelling of the endosomal-lysosomal systems. The heavily melanized melanosomes did not have an altered shape, which suggests a lesser degree of membrane dynamics of stage IV melanosomes. Terminal lysosomes loaded with TR-dextran are also distinct from melanosomes, thus indicating that melanosomes are isolated from the endocytic pathway that is a representative route to lysosomes. Because AP-3 mutation leads to mistargeting of both melanosome and lysosome membrane proteins, we propose that there is a late sorting step for melanosomes and lysosomes in melanocytes after AP-3 sorting.
Fujita
H
H
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Sasano
E
E
Yasunaga
K
K
Furuta
K
K
Yokota
S
S
Wada
I
I
Himeno
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D020460:Melanosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D010088:Oxidoreductases; D021381:Protein Transport / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000502:physiology / Q000648:ultrastructure; D000077191:Wortmannin
D000730:Androstadienes; D015703:Antigens, CD; D018955:CD36 Antigens; D004791:Enzyme Inhibitors; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; C489452:Scarb2 protein, mouse; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D000077191:Wortmannin