Endocytic pathway from the basal plasma membrane to the ruffled border membrane in bone-resorbing osteoclasts

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摘要：

We have characterized the convoluted ruffled border (RB) membrane that an activated osteoclast maintains against the bone matrix. The bulk of both lgp110 and rab7, a small GTP-binding protein participating in vesicle fusion to late endosomes, was localized to the RB. This indicates that the membrane has some characteristics of late endosomal membranes in other cells. Furthermore, the bulk of membrane-bound rab7 on the RB suggests that endocytic membrane transport is oriented towards the RB in resorbing osteoclasts. Consistently, both lumenal horseradish peroxidase and receptor-bound transferrin, a marker of the early endosomal recycling pathway, were efficiently endocytosed from the basal plasma membrane and delivered to the RB. Delivery of membrane-associated transferrin to the RB further indicates that the RB is compositionally different from lysosomes and suggests that the endocytic pathway contributes to the maintenance of functional RB. In addition to transporting receptor-bound cargo to the RB, the endocytic pathway could act in balancing the membrane traffic associated with transcytosis from the RB to the basal plasma membrane. Endocytic processes (retrieval of mannose 6-phosphate receptors) in osteoclasts appeared to be fairly sensitive to bafilomycin A1, a specific inhibitor of vacuolar-type proton ATPases. Thus blocking the endocytic membrane traffic towards the RB could explain the inactivation of cells by low concentrations of the drug.

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关键词：

Bafilomycin a(1) Bone resorption Endosome Osteoclast Mannose 6-phosphate receptors Vacuolar proton pump Trans-golgi network Canine kidney-cells Late endosomes Lysosomal-enzymes Vitronectin receptor H+-atpases Resorption Proteins