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DeSelm, Carl J.; Miller, Brian C.; Zou, Wei; Beatty, Wandy L.; van Meel, Eline; Takahata, Yoshifumi; Klumperman, Judith; Tooze, Sharon A.; Teitelbaum, Steven L.; Virgin, Herbert W.
Developmental cell, 11/2011, Letnik: 21, Številka: 5Journal Article
Osteoclasts resorb bone via the ruffled border, whose complex folds are generated by secretory lysosome fusion with bone-apposed plasma membrane. Lysosomal fusion with the plasmalemma results in acidification of the resorptive microenvironment and release of CatK to digest the organic matrix of bone. The means by which secretory lysosomes are directed to fuse with the ruffled border are enigmatic. We show that proteins essential for autophagy, including Atg5, Atg7, Atg4B, and LC3, are important for generating the osteoclast ruffled border, the secretory function of osteoclasts, and bone resorption in vitro and in vivo. Further, Rab7, which is required for osteoclast function, localizes to the ruffled border in an Atg5-dependent manner. Thus, autophagy proteins participate in polarized secretion of lysosomal contents into the extracellular space by directing lysosomes to fuse with the plasma membrane. These findings are in keeping with a putative link between autophagy genes and human skeletal homeostasis. Display omitted ► Polarized lysosomal secretion by osteoclasts requires Atg5, Atg7, Atg4B, and LC3 ► LC3 localization to the ruffled border depends on Atg5 and LC3 lipidation ► Atg5 is important for Rab7 localization to the ruffled border and its formation ► Osteoclast function requires Atg5 in vitro and in vivo
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in: SICRIS
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