|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Journal of Experimental Biology, Vol 172, Issue 1 193-204, Copyright © 1992 by Company of Biologists
JOURNAL ARTICLES |
D Chatterjee, M Chakraborty, M Leit, L Neff, S Jamsa-Kellokumpu, R Fuchs, M Bartkiewicz, N Hernando and R Baron
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
Osteoclasts are multinucleated cells derived from the mononuclear phagocyte system in the hematopoietic bone marrow. Their function is to resorb bone during skeletal growth and remodeling. They perform this function by acidifying an enclosed extracellular space, the bone resorbing compartment. Analysis of proton transport by inside-out vesicles derived from highly purified chicken osteoclast membranes has revealed the presence of a novel type of multisubunit vacuolar-like H(+)-ATPase. Unlike H(+)-ATPases derived from any other cell type or organelle, proton transport and ATPase activity in osteoclast vesicles are sensitive to two classes of inhibitors, namely V-ATPase inhibitors [N-ethyl-maleimide (NEM) and bafilomycin A1] and vanadate (IC50 100 mumol l-1), an inhibitor previously found to affect only P-ATPases. The osteoclast V-ATPase morphologically resembles vacuolar proton pumps and contains several vacuolar-like subunits (115 x 10(3), 39 x 10(3) and 16 x 10(3)M(r)), demonstrated by Western blot analysis. Subunits A and B of the catalytic domain of the enzyme, however, differ from that of other V-ATPases. In osteoclasts, subunit A has an M(r) of 63 x 10(3) instead of 67 x 10(3)-70 x 10(3); in contrast, monocytes, macrophages and kidney microsomes, which contain a vanadate-insensitive H(+)-ATPase, express the classical subunit A (70 x 10(3)M(r)). Moreover, two types of 57 x 10(3)-60 x 10(3)M(r) B subunits are also found: they are differentially recognized by antibodies and one is expressed predominantly in osteoclasts and the other in bone marrow cells and in kidney microsomes. Preliminary cloning data have indicated that the B subunit expressed in osteoclasts may be similar to the brain isoform. The osteoclast proton pump may, therefore, constitute a novel class of V-ATPase, with a unique pharmacology and specific isoforms of two subunits in the catalytic portion of the enzyme.
This article has been cited by other articles:
|
|
 |
|
  B. F. BOYCE, L. XING, Z. YAO, W. C. SHAKESPEARE, Y. WANG, C. A. METCALF III, R. SUNDARAMOORTHI, D. C. DALGARNO, J. D. IULIUCCI, and T. K. SAWYER Future Anti-Catabolic Therapeutic Targets in Bone Disease Ann. N.Y. Acad. Sci., April 1, 2006; 1068(1): 447 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Futai, T Oka, G Sun-Wada, Y Moriyama, H Kanazawa, and Y Wada Luminal acidification of diverse organelles by V-ATPase in animal cells J. Exp. Biol., January 1, 2000; 203(1): 107 - 116. [Abstract]
|
|
|
|
 |
|
 T. Oka, R. Yamamoto, and M. Futai Multiple Genes for Vacuolar-type ATPase Proteolipids in Caenorhabditis elegans. A NEW GENE, vha-3, HAS A DISTINCT CELL-SPECIFIC DISTRIBUTION J. Biol. Chem., August 28, 1998; 273(35): 22570 - 22576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Muller, U. Irkens-Kiesecker, D. Kramer, and L. Taiz Purification and Reconstitution of the Vacuolar H+-ATPases from Lemon Fruits and Epicotyls J. Biol. Chem., May 9, 1997; 272(19): 12762 - 12770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Müller, U. Irkens-Kiesecker, B. Rubinstein, and L. Taiz On the Mechanism of Hyperacidification in Lemon J. Biol. Chem., January 26, 1996; 271(4): 1916 - 1924. [Abstract] [Full Text] [PDF]
|
|
