biostudies-literatureCremasco VIntramural NIH HHSNIBIB NIH HHSNIAMS NIH HHS2452-63https://www.ebi.ac.uk/biostudies/studies/S-EPMC3498518biostudies-literatureUnknown27(12)Bone homeostasis requires stringent regulation of osteoclasts, which secrete proteolytic enzymes to degrade the bone matrix. Despite recent progress in understanding how bone resorption occurs, the mechanisms regulating osteoclast secretion, and in particular the trafficking route of cathepsin K vesicles, remain elusive. Using a genetic approach, we describe the requirement for protein kinase C-delta (PKCδ) in regulating bone resorption by affecting cathepsin K exocytosis. Importantly, PKCδ deficiency does not perturb formation of the ruffled border or trafficking of lysosomal vesicles containing the vacuolar-ATPase (v-ATPase). Mechanistically, we find that cathepsin K exocytosis is controlled by PKCδ through modulation of the actin bundling protein myristoylated alanine-rich C-kinase subsJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral ResearchProtein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts.PMC3498518T32 AR060719ZIA ES090092-12R01 AR052705AR052705P30AR057235R01 AR053628P30 AR057235R21 EB0075685R01 AR053628EB007568Lupu TSFaccio RCremasco VStumpo DNakayama KIDecker CENovack DVNakayama KBlackshear PJGraham DBfalseProtein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts.Bone homeostasis requires stringent regulation of osteoclasts, which secrete proteolytic enzymes to degrade the bone matrix. Despite recent progress in understanding how bone resorption occurs, the mechanisms regulating osteoclast secretion, and in particular the trafficking route of cathepsin K vesicles, remain elusive. Using a genetic approach, we describe the requirement for protein kinase C-delta (PKCδ) in regulating bone resorption by affecting cathepsin K exocytosis. Importantly, PKCδ deficiency does not perturb formation of the ruffled border or trafficking of lysosomal vesicles containing the vacuolar-ATPase (v-ATPase). Mechanistically, we find that cathepsin K exocytosis is controlled by PKCδ through modulation of the actin bundling protein myristoylated alanine-rich C-kinase subs2012-01-01T00:00:00Z2012 Dec2025-04-04T01:06:21.693Z2019-03-27T01:00:33ZS-EPMC34985182280693510.1002/jbmr.1701