AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis.
Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type-specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation. Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1- and KIF13A-dependent dynamic close appositions and continuities between peripheral endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is coupled to cell type-specific positioning of endosomes that facilitate endosome-LRO contacts and are required for organelle maturation.
Delevoye
Cédric
C
Structure and Membrane Compartments, Centre Nationale de la Recherche Scientifique, UMR 144 Institut Curie, Centre de Recherche, Paris F-75248, France.
Hurbain
Ilse
I
Tenza
Danièle
D
Sibarita
Jean-Baptiste
JB
Uzan-Gafsou
Stéphanie
S
Ohno
Hiroshi
H
Geerts
Willie J C
WJ
Verkleij
Arie J
AJ
Salamero
Jean
J
Marks
Michael S
MS
Raposo
Graça
G
D002460:Cell Line; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D034741:RNA, Small Interfering / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
C417670:KIF13A protein, human; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D016547:Kinesins