Journal
DEVELOPMENTAL CELL
Volume 21, Issue 5, Pages 966-974Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2011.08.016
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Funding
- National Institutes of Health [AG032795]
- Netherlands Organization for Scientific Research (NWO) [918.56.611]
- [RO1 A10848887]
- [U54 A1057160]
- [AR057235]
- [AR032788]
- [AR057037]
- [AR046523]
- [AR054618]
- Grants-in-Aid for Scientific Research [09J03309] Funding Source: KAKEN
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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.
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