Selective internalization of the apical plasma membrane and rapid redistribution of lysosomal enzymes and mannose 6-phosphate receptors during osteoclast inactivation by calcitonin.
The effects of inhibition of bone resorption by the peptide hormone calcitonin have been studied at the level of the osteoclast. Although not epithelial, the osteoclast is polarized with the secretion of newly synthesized lysosomal enzymes and of acid occurring specifically at the apical pole, facing the bone compartment. The membranes composing the apical (ruffled-border) and basolateral domains contain topologically restricted antigens, a 100 x 10(3) Mr lysosomal membrane protein and the Na+,K(+)-ATPase, respectively. It was found that calcitonin induces a rapid (15-60 min) redistribution of the apical marker as well as of markers of the secretory compartment of the osteoclast (arylsulfatase and cation-independent mannose 6-phosphate (Man6P) receptors). The apical plasma membrane, in contrast to the basolateral membrane, is selectively internalized. This internalization leads to the disappearance of the ruffled border. The vesicular translocation of apical membranes is reminiscent of the events occurring in gastric oxyntic cells and in kidney tubule intercalated cells during the regulation of acid secretion. In parallel, the synthesis of both the lysosomal enzyme arylsulfatase and Man6P receptors is arrested. The products that were already present in the secretory pathway seem to be rerouted to intracellular vacuoles instead of being targeted to the plasma membrane, leading to marked accumulation of enzymes in the inhibited cells. These results suggest that the rapid inhibition of bone resorption by calcitonin involves the vesicular translocation of the apical membranes and the rapid arrest in the synthesis and secretion of lysosomal enzymes in osteoclasts.
Baron
R
R
Yale University School of Medicine, Department of Cell Biology, New Haven, CT 06510.
Neff
L
L
Brown
W
W
Louvard
D
D
Courtoy
P J
PJ
D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002116:Calcitonin / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D006651:Histocytochemistry; D007150:Immunohistochemistry; D008247:Lysosomes / Q000201:enzymology*; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013997:Time Factors
D015415:Biomarkers; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D002116:Calcitonin