Disruption of the Man-6-P targeting pathway in mice impairs osteoclast secretory lysosome biogenesis.

ABSTRACT: Osteoclasts are specialized cells that secrete lysosomal acid hydrolases at the site of bone resorption, a process critical for skeletal formation and remodeling. However, the cellular mechanism underlying this secretion and the organization of the endo-lysosomal system of osteoclasts have remained unclear. We report that osteoclasts differentiated in vitro from murine bone marrow macrophages contain two types of lysosomes. The major species is a secretory lysosome containing cathepsin K and tartrate-resistant acid phosphatase (TRAP), two hydrolases critical for bone resorption. These secretory lysosomes are shown to fuse with the plasma membrane, allowing the regulated release of acid hydrolases at the site of bone resorption. The other type of lysosome contains cathepsin D, but little ca

SUBMITTER: van Meel E 

PROVIDER: S-EPMC3115509 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature