Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border

doi:10.1083/jcb.101.6.2210

This Article

	Full Text (PDF, 2180K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Baron, R.
	Articles by Courtoy, P. J.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Baron, R.
	Articles by Courtoy, P. J.

Social Bookmarking

	What's this?

ARTICLES

Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border

R Baron, L Neff, D Louvard and PJ Courtoy

The extracellular compartment where bone resorption occurs, between the osteoclast and bone matrix, is shown in this report to be actively acidified. The weak base acridine orange accumulates within this compartment but dissipates after incubation with ammonium chloride. Upon removal of ammonium chloride, the cells are able to rapidly reacidify this compartment. The highly convoluted plasma membrane of the osteoclast facing this acidic compartment (ruffled border) is shown to contain a 100-kD integral membrane protein otherwise present in limiting membranes of lysosomes and other related acidified organelles (Reggio, H., D. Bainton, E. Harms, E. Coudrier, and D. Louvard, 1984, J. Cell Biol., 99:1511-1526; Tougard, C., D. Louvard, R. Picart, and A. Tixier-Vidal, 1985, J. Cell Biol. 100:786-793). Antibodies recognizing this 100-kD lysosomal membrane protein cross-react with a proton-pump ATPase from pig gastric mucosae (Reggio, H., D. Bainton, E. Harms, E. Coudrier, and D. Louvard, 1984, J. Cell Biol., 99:1511-1526), therefore raising the possibility that it plays a role in the acidification of both intracellular organelles and extracellular compartments. Lysosomal enzymes are also directionally secreted by the osteoclast into the acidified extracellular compartment which can therefore be considered as the functional equivalent of a secondary lysosome with a low pH, acid hydrolases, the substrate, and a limiting membrane containing the 100-kD antigen.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Wu, J., Glimcher, L. H., Aliprantis, A. O. (2008). HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function. Proc. Natl. Acad. Sci. USA 105: 16934-16939 [Abstract] [Full Text]
Feng, H., Cheng, T., Pavlos, N. J., Yip, K. H. M., Carrello, A., Seeber, R., Eidne, K., Zheng, M. H., Xu, J. (2008). Cytoplasmic Terminus of Vacuolar Type Proton Pump Accessory Subunit Ac45 Is Required for Proper Interaction with V0 Domain Subunits and Efficient Osteoclastic Bone Resorption. J. Biol. Chem. 283: 13194-13204 [Abstract] [Full Text]
Okamoto, F., Kajiya, H., Toh, K., Uchida, S., Yoshikawa, M., Sasaki, S., Kido, M. A., Tanaka, T., Okabe, K. (2008). Intracellular ClC-3 chloride channels promote bone resorption in vitro through organelle acidification in mouse osteoclasts. Am. J. Physiol. Cell Physiol. 294: C693-C701 [Abstract] [Full Text]
Bouyer, P., Sakai, H., Itokawa, T., Kawano, T., Fulton, C. M., Boron, W. F., Insogna, K. L. (2007). Colony-Stimulating Factor-1 Increases Osteoclast Intracellular pH and Promotes Survival via the Electroneutral Na/HCO3 Cotransporter NBCn1. Endocrinology 148: 831-840 [Abstract] [Full Text]
Piwnica, D., Fernandez, I., Binart, N., Touraine, P., Kelly, P. A., Goffin, V. (2006). A New Mechanism for Prolactin Processing into 16K PRL by Secreted Cathepsin D. Mol. Endocrinol. 20: 3263-3278 [Abstract] [Full Text]
Cui, M., Honore, P., Zhong, C., Gauvin, D., Mikusa, J., Hernandez, G., Chandran, P., Gomtsyan, A., Brown, B., Bayburt, E. K., Marsh, K., Bianchi, B., McDonald, H., Niforatos, W., Neelands, T. R., Moreland, R. B., Decker, M. W., Lee, C.-H., Sullivan, J. P., Faltynek, C. R. (2006). TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists.. J. Neurosci. 26: 9385-9393 [Abstract] [Full Text]
Woo, J.-T., Kawatani, M., Kato, M., Shinki, T., Yonezawa, T., Kanoh, N., Nakagawa, H., Takami, M., Lee, K. H., Stern, P. H., Nagai, K., Osada, H. (2006). Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts. Proc. Natl. Acad. Sci. USA 103: 4729-4734 [Abstract] [Full Text]
Czupalla, C., Mansukoski, H., Riedl, T., Thiel, D., Krause, E., Hoflack, B. (2006). Proteomic Analysis of Lysosomal Acid Hydrolases Secreted by Osteoclasts: Implications for Lytic Enzyme Transport and Bone Metabolism. Mol. Cell. Proteomics 5: 134-143 [Abstract] [Full Text]
Sun, Y., Buki, K. G., Ettala, O., Vaaraniemi, J. P., Vaananen, H. K. (2005). Possible Role of Direct Rac1-Rab7 Interaction in Ruffled Border Formation of Osteoclasts. J. Biol. Chem. 280: 32356-32361 [Abstract] [Full Text]
Honore, P., Wismer, C. T., Mikusa, J., Zhu, C. Z., Zhong, C., Gauvin, D. M., Gomtsyan, A., El Kouhen, R., Lee, C.-H., Marsh, K., Sullivan, J. P., Faltynek, C. R., Jarvis, M. F. (2005). A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a Novel Transient Receptor Potential Type V1 Receptor Antagonist, Relieves Pathophysiological Pain Associated with Inflammation and Tissue Injury in Rats. J. Pharmacol. Exp. Ther. 314: 410-421 [Abstract] [Full Text]
Bruzzaniti, A., Neff, L., Sanjay, A., Horne, W. C., De Camilli, P., Baron, R. (2005). Dynamin Forms a Src Kinase-sensitive Complex with Cbl and Regulates Podosomes and Osteoclast Activity. Mol. Biol. Cell 16: 3301-3313 [Abstract] [Full Text]
Karsdal, M. A., Henriksen, K., Sorensen, M. G., Gram, J., Schaller, S., Dziegiel, M. H., Heegaard, A.-M., Christophersen, P., Martin, T. J., Christiansen, C., Bollerslev, J. (2005). Acidification of the Osteoclastic Resorption Compartment Provides Insight into the Coupling of Bone Formation to Bone Resorption. Am. J. Pathol. 166: 467-476 [Abstract] [Full Text]
Abedin, M., Tintut, Y., Demer, L. L. (2004). Vascular Calcification: Mechanisms and Clinical Ramifications. Arterioscler. Thromb. Vasc. Bio. 24: 1161-1170 [Abstract] [Full Text]
Henriksen, K., Gram, J., Schaller, S., Dahl, B. H., Dziegiel, M. H., Bollerslev, J., Karsdal, M. A. (2004). Characterization of Osteoclasts from Patients Harboring a G215R Mutation in ClC-7 Causing Autosomal Dominant Osteopetrosis Type II. Am. J. Pathol. 164: 1537-1545 [Abstract] [Full Text]
Taranta, A., Migliaccio, S., Recchia, I., Caniglia, M., Luciani, M., De Rossi, G., Dionisi-Vici, C., Pinto, R. M., Francalanci, P., Boldrini, R., Lanino, E., Dini, G., Morreale, G., Ralston, S. H., Villa, A., Vezzoni, P., Del Principe, D., Cassiani, F., Palumbo, G., Teti, A. (2003). Genotype-Phenotype Relationship in Human ATP6i-Dependent Autosomal Recessive Osteopetrosis. Am. J. Pathol. 162: 57-68 [Abstract] [Full Text]
Parikka, V., Lehenkari, P., Sassi, M.-L., Halleen, J., Risteli, J., Harkonen, P., Vaananen, H. K. (2001). Estrogen Reduces the Depth of Resorption Pits by Disturbing the Organic Bone Matrix Degradation Activity of Mature Osteoclasts. Endocrinology 142: 5371-5378 [Abstract] [Full Text]
Zhao, H., Laitala-Leinonen, T., Parikka, V., Vaananen, H. K. (2001). Downregulation of Small GTPase Rab7 Impairs Osteoclast Polarization and Bone Resorption. J. Biol. Chem. 276: 39295-39302 [Abstract] [Full Text]
Sobacchi, C., Frattini, A., Orchard, P., Porras, O., Tezcan, I., Andolina, M., Babul-Hirji, R., Baric, I., Canham, N., Chitayat, D., Dupuis-Girod, S., Ellis, I., Etzioni, A., Fasth, A., Fisher, A., Gerritsen, B., Gulino, V., Horwitz, E., Klamroth, V., Lanino, E., Mirolo, M., Musio, A., Matthijs, G., Nonomaya, S., Notarangelo, L. D., Ochs, H. D., Superti Furga, A., Valiaho, J., van Hove, J. L.K., Vihinen, M., Vujic, D., Vezzoni, P., Villa, A. (2001). The mutational spectrum of human malignant autosomal recessive osteopetrosis. Hum Mol Genet 10: 1767-1773 [Abstract] [Full Text]
Punturieri, A., Filippov, S., Allen, E., Caras, I., Murray, R., Reddy, V., Weiss, S. J. (2000). Regulation of Elastinolytic Cysteine Proteinase Activity in Normal and Cathepsin K-Deficient Human Macrophages. JEM 192: 789-800 [Abstract] [Full Text]
Salahifar, H., Baxter, R. C., Martin, J. L. (2000). Differential Regulation of Insulin-Like Growth Factor-Binding Protein-3 Protease Activity in MCF-7 Breast Cancer Cells by Estrogen and Transforming Growth Factor-{beta}1. Endocrinology 141: 3104-3110 [Abstract] [Full Text]
Kornak, U., Schulz, A., Friedrich, W., Uhlhaas, S., Kremens, B., Voit, T., Hasan, C., Bode, U., Jentsch, T. J., Kubisch, C. (2000). Mutations in the a3 subunit of the vacuolar H+-ATPase cause infantile malignant osteopetrosis. Hum Mol Genet 9: 2059-2063 [Abstract] [Full Text]
Vaananen, H., Zhao, H, Mulari, M, Halleen, J. (2000). The cell biology of osteoclast function. J. Cell Sci. 113: 377-381 [Abstract]
Jimi, E., Akiyama, S., Tsurukai, T., Okahashi, N., Kobayashi, K., Udagawa, N., Nishihara, T., Takahashi, N., Suda, T. (1999). Osteoclast Differentiation Factor Acts as a Multifunctional Regulator in Murine Osteoclast Differentiation and Function. J. Immunol. 163: 434-442 [Abstract] [Full Text]
Laitala-Leinonen, T, Lowik, C, Papapoulos, S, Vaananen, H. (1999). Inhibition of intravacuolar acidification by antisense RNA decreases osteoclast differentiation and bone resorption in vitro. J. Cell Sci. 112: 3657-3666 [Abstract]
Nakamura, I., Tanaka, H., Rodan, G. A., Duong, L. T. (1998). Echistatin Inhibits the Migration of Murine Prefusion Osteoclasts and the Formation of Multinucleated Osteoclast-Like Cells. Endocrinology 139: 5182-5193 [Abstract] [Full Text]
Jimi, E., Nakamura, I., Ikebe, T., Akiyama, S., Takahashi, N., Suda, T. (1998). Activation of NF-kappa B Is Involved in the Survival of Osteoclasts Promoted by Interleukin-1. J. Biol. Chem. 273: 8799-8805 [Abstract] [Full Text]
Marathe, S., Schissel, S. L., Yellin, M. J., Beatini, N., Mintzer, R., Williams, K. J., Tabas, I. (1998). Human Vascular Endothelial Cells Are a Rich and Regulatable Source of Secretory Sphingomyelinase. IMPLICATIONS FOR EARLY ATHEROGENESIS AND CERAMIDE-MEDIATED CELL SIGNALING. J. Biol. Chem. 273: 4081-4088 [Abstract] [Full Text]
Roussa, E., Thevenod, F., Sabolic, I., Herak-Kramberger, C. M., Nastainczyk, W., Bock, R., Schulz, I. (1998). Immunolocalization of Vacuolar-type H+-ATPase in Rat Submandibular Gland and Adaptive Changes Induced by Acid-Base Disturbances. J. Histochem. Cytochem. 46: 91-100 [Abstract] [Full Text]
Schlesinger, P. H., Blair, H. C., Teitelbaum, S. L., Edwards, J. C. (1997). Characterization of the Osteoclast Ruffled Border Chloride Channel and Its Role in Bone Resorption. J. Biol. Chem. 272: 18636-18643 [Abstract] [Full Text]
Godwin, S. L., Soltoff, S. P. (1997). Extracellular Calcium and Platelet-derived Growth Factor Promote Receptor-mediated Chemotaxis in Osteoblasts through Different Signaling Pathways. J. Biol. Chem. 272: 11307-11312 [Abstract] [Full Text]
Inui, T., Ishibashi, O., Inaoka, T., Origane, Y., Kumegawa, M., Kokubo, T., Yamamura, T. (1997). Cathepsin K Antisense Oligodeoxynucleotide Inhibits Osteoclastic Bone Resorption. J. Biol. Chem. 272: 8109-8112 [Abstract] [Full Text]
Bonewald, L. F., Oreffo, R. O. C., Lee, C. H., Park-Snyder, S., Twardzik, D., Mundy, G. R. (1997). Effects of Retinol on Activation of Latent Transforming Growth Factor-{beta} by Isolated Osteoclasts. Endocrinology 138: 657-666 [Abstract] [Full Text]
Palokangas, H, Mulari, M, Vaananen, H. (1997). Endocytic pathway from the basal plasma membrane to the ruffled border membrane in bone-resorbing osteoclasts. J. Cell Sci. 110: 1767-1780 [Abstract]
Tourkin, A, Bonner, M, Mantrova, E, LeRoy, E., Hoffman, S (1996). Dot-like focal contacts in adherent eosinophils, their redistribution into peripheral belts, and correlated effects on cell migration and protected zone formation. J. Cell Sci. 109: 2169-2177 [Abstract]
Salo, J, Metsikko, K, Palokangas, H, Lehenkari, P, Vaananen, H. (1996). Bone-resorbing osteoclasts reveal a dynamic division of basal plasma membrane into two different domains. J. Cell Sci. 109: 301-307 [Abstract]
Nordstr�m, T., Rotstein, O. D., Romanek, R., Asotra, S., Heersche, J. N. M., Manolson, M. F., Brisseau, G. F., Grinstein, S. (1995). Regulation of Cytoplasmic pH in Osteoclasts. J. Biol. Chem. 270: 2203-2212 [Abstract] [Full Text]
Hill, P., Murphy, G, Docherty, A., Hembry, R., Millican, T., Reynolds, J., Meikle, M. (1994). The effects of selective inhibitors of matrix metalloproteinases (MMPs) on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts. J. Cell Sci. 107: 3055-3064 [Abstract]
Montcourrier, P, Mangeat, P., Valembois, C, Salazar, G, Sahuquet, A, Duperray, C, Rochefort, H (1994). Characterization of very acidic phagosomes in breast cancer cells and their association with invasion. J. Cell Sci. 107: 2381-2391 [Abstract]
Delaisse, J., Eeckhout, Y, Neff, L, Francois-Gillet, C, Henriet, P, Su, Y, Vaes, G, Baron, R (1993). (Pro)collagenase (matrix metalloproteinase-1) is present in rodent osteoclasts and in the underlying bone-resorbing compartment. J. Cell Sci. 106: 1071-1082 [Abstract]
Sasaki, T., Ueno-Matsuda, E. (1992). Immunocytochemical Localization of Cathepsins B and G in Odontoclasts of Human Deciduous Teeth. JDR 71: 1881-1884 [Abstract]
Blair, H., Teitelbaum, S., Ghiselli, R, Gluck, S (1989). Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 245: 855-857 [Abstract]
Kellokumpu, S, Neff, L, Jamsa-Kellokumpu, S, Kopito, R, Baron, R (1988). A 115-kD polypeptide immunologically related to erythrocyte band 3 is present in Golgi membranes. Science 242: 1308-1311 [Abstract]
Morikawa, W., Yamamoto, K., Ishikawa, S., Takemoto, S., Ono, M., Fukushi, J.-i., Naito, S., Nozaki, C., Iwanaga, S., Kuwano, M. (2000). Angiostatin Generation by Cathepsin D Secreted by Human Prostate Carcinoma Cells. J. Biol. Chem. 275: 38912-38920 [Abstract] [Full Text]
James, I. E., Marquis, R. W., Blake, S. M., Hwang, S. M., Gress, C. J., Ru, Y., Zembryki, D., Yamashita, D. S., McQueney, M. S., Tomaszek, T. A., Oh, H.-J., Gowen, M., Veber, D. F., Lark, M. W. (2001). Potent and Selective Cathepsin L Inhibitors Do Not Inhibit Human Osteoclast Resorption in Vitro. J. Biol. Chem. 276: 11507-11511 [Abstract] [Full Text]