Abstract
The osteoclast is a polarized cell which secretes large amounts of newly synthesized lysosomal enzymes into an apical extracellular lacuna where bone resorption takes place. Using immunocytochemical techniques, we have localized the cation-independent mannose-6-phosphate (Man6P) receptor and lysosomal enzymes in this cell type in order to determine the expression and distribution of this receptor and its ligands. The results demonstrate that the osteoclast expresses large amounts of immunoreactive cation-independent Man6P receptors, despite the fact that most of the lysosomal enzymes it synthesizes are secreted. The lysosomal enzymes and the receptors are co-distributed along the exocytic pathway, i.e., the endoplasmic reticulum, including the perinuclear envelope, the Golgi stacks as well as numerous small transport vesicles that appear to fuse with the ruffled border membrane. Within the Golgi complex, the receptors and lysosomal enzymes were found distributed in two predominant patterns; (a) in all the cisternae, from cis to trans, or (b) predominantly in cis- and trans-Golgi cisternae, with the middle Golgi cisternae being unstained or depleted in antigen. This pattern suggests that enzymes and receptors traverse the Golgi from cis to trans and preferentially accumulate in cis- and in trans-cisternae. This study therefore suggests that, in the osteoclast, Man6P receptors are involved in the vectorial transport and targeting of newly synthesized lysosomal enzymes, presumably via a constitutive pathway, to the apical membrane where they are secreted into the bone-resorbing compartment. This mechanism could insure polarized secretion of lysosomal enzymes into the bone-resorbing lacuna.
Highlights
The osteoclast is a polarized cell which secretes large amounts of newly synthesized lysosomal enzymes into an apical extracellular lacuna where bone resorption takes place
As previously reported [2], arylsulfatase and beta-glycerophosphatase were found by enzyme cytochemistry all along the exocytic pathway: in the endoplasmic reticulum (ER), in all Golgi stacks, and in coated transport vesicles which appeared to fuse with the apical plasma membrane at the ruffled border (Figs. 2, A-D, and 3 A)
Cathepsin C and beta-glucuronidase were found in the lysosomes of every cell type present in these bone sections, thereby demonstrating that the antigens were appropriately recognized by the antibodies in our preparations
Summary
The osteoclast is a polarized cell which secretes large amounts of newly synthesized lysosomal enzymes into an apical extracellular lacuna where bone resorption takes place. This study suggests that, in the osteoclast, Man6P receptors are involved in the vectorial transport and targeting of newly synthesized lysosomal enzymes, presumably via a constitutive pathway, to the apical membrane where they are secreted into the bone-resorbing compartment. This mechanism could insure polarized secretion of lysosomal enzymes into the bone-resorbing lacuna. I N most cell types, lysosomal enzymes are synthesized in the endoplasmic reticulum, glycosylated in the Golgi complex, and transported to an intracellular prelysosomal delivery site, most recently identified as a late compartment of the endosomal system [10]. The Journal of Cell Biology, Volume 106, June 1988 1863-1872 the N-linked high mannose sugars of newly synthesized lysosomal enzymes are phosphorylated in the cis-cisternaeof the
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