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 - Funding Information:
This work was supported by National Institutes of Health grants R01 EY015625 (to M.S. Marks and G. Raposo) and P30 EY001583 from the National Eye Institute and R01 GM108807 from the National Institute of General Medical Sciences (to M.S. Marks), the Institut Curie and Centre National de la Recherche Scientifique (to G. Raposo), Wellcome Trust grant 078327 (to E.V. Sviderskaya and D.C. Bennett), postdoctoral fellowship 0625437U from the American Heart Association and Wellcome Trust-Department of Biotechnology India Alliance Senior Fellowship 500122/Z/09/Z (to S.R.G. Setty), and Institutional Research and Academic Career Development Award postdoctoral fellowship K12 GM081259 and National Institutes of Health grant F32 AR062476 (to M.K. Dennis).
Publisher Copyright:
© 2015 Dennis et al.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
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
VL - 209
SP - 563
EP - 577
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 4
ER -