Palokangas H, Mulari M, Väänänen H K
Department of Anatomy and Biocenter, University of Oulu, Finland.
J Cell Sci. 1997 Aug;110 ( Pt 15):1767-80. doi: 10.1242/jcs.110.15.1767.
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.
我们已对活化破骨细胞与骨基质相对的卷曲褶皱边缘（RB）膜进行了表征。参与囊泡与晚期内体融合的小GTP结合蛋白lgp110和rab7的大部分都定位于RB。这表明该膜具有其他细胞中晚期内体膜的一些特征。此外，RB上大部分膜结合的rab7表明，在吸收性破骨细胞中，内吞膜运输是朝向RB的。一致地，管腔辣根过氧化物酶和受体结合转铁蛋白（早期内体循环途径的标志物）都从基底质膜有效地内吞并传递到RB。膜相关转铁蛋白向RB的传递进一步表明RB在组成上与溶酶体不同，并表明内吞途径有助于功能性RB的维持。除了将受体结合的货物运输到RB外，内吞途径还可以平衡与从RB到基底质膜的转胞吞作用相关的膜运输。破骨细胞中的内吞过程（甘露糖6 - 磷酸受体的回收）似乎对液泡型质子ATP酶的特异性抑制剂巴弗洛霉素A1相当敏感。因此，阻断朝向RB的内吞膜运输可以解释低浓度药物使细胞失活的现象。
