TY - JOUR
T1 - BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
AU - Dennis, Megan K.
AU - Mantegazza, Adriana R.
AU - Snir, Olivia L.
AU - Tenza, Danièle
AU - Acosta-Ruiz, Amanda
AU - Delevoye, Cédric
AU - Zorger, Richard
AU - Sitaram, Anand
AU - de Jesus-Rojas, Wilfredo
AU - Ravichandran, Keerthana
AU - Rux, John
AU - Sviderskaya, Elena V.
AU - Bennett, Dorothy C.
AU - Raposo, Graça
AU - Marks, Michael S.
AU - Setty, Subba Rao Gangi
N1 - Publisher Copyright:
© 2015 Dennis et al.
PY - 2015
Y1 - 2015
N2 - Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2-deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2-deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation.
AB - Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2-deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2-deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation.
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U2 - 10.1083/jcb.201410026
DO - 10.1083/jcb.201410026
M3 - Article
C2 - 26008744
AN - SCOPUS:84946083746
SN - 0021-9525
VL - 209
SP - 563
EP - 577
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -