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J. Biol. Chem., Vol. 278, Issue 20, 18573-18580, May 16, 2003
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From the Membrane lipid rafts play a key role in immune
cell activation by recruiting and excluding specific signaling
components of immune cell surface receptors upon the receptor
engagement. Despite this, the role of these microdomains in the
regulation of osteoclasts as controlled by receptor activator of
nuclear factor
Membrane Rafts Play a Crucial Role in Receptor
Activator of Nuclear Factor
B Signaling and Osteoclast
Function*
§,§¶,§¶,
,§¶, and§¶§§
National Research Laboratory for Bone
Metabolism, ¶ Research Center for Proteineous Materials, and
§ School of Dentistry, Chosun University, Gwangju 501-759, Korea, the Department of Biochemistry, University of Ulsan
College of Medicine, Seoul 138-736, Korea, and the
** Department of Haematology, Faculty of Medicine,
Imperial College of Science, Technology and Medicine, Hammersmith
Hospital, London W12 ONN, United Kingdom
B (RANK) has yet to be established. In this study, we
demonstrate that the raft microdomain expression plays an essential
role in osteoclast function and differentiation. Expression of raft
component flotillin greatly increased during osteoclast
differentiation, whereas engagement of RANK induced the translocation
of tumor necrosis factor receptor-associated factor 6 to rafts where
Src was constitutively resident. Disruption of rafts blocked TRAF6
translocation and Akt activation by RANK ligand in osteoclasts and
further reduced the survival of osteoclasts. Actin ring formation and
bone resorption by osteoclasts were also found to require the integrity
of rafts. Our observations demonstrate for the first time that
RANK-mediated signaling and osteoclast function are critically
dependent on the expression and integrity of raft membrane microdomains.
*
This work was supported by grants from the Ministry of
Science and Technology, Korea and the Korea Science and Engineering Foundation through the Research Center for Proteineous Materials, the
National Research Laboratory, and 21C Frontier Functional Proteomics Project Grant FPR02A3-5-110.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed: Chosun University
School of Dentistry, 375 Seosuk-Dong, Dong-Gu, Gwangju 501-759, Korea.
Tel.: 82-62-230-6853; Fax: 82-62-227-6589; E-mail:
jhblee@chosun.ac.kr.
§§
To whom correspondence may be addressed: College of Dentistry,
Seoul National University, Seoul 110-749, Korea. Tel.:
82-2-740-8686; Fax: 82-2-765-8656; E-mail: hhbkim@snu.ac.kr or
hhbkim{at}yahoo.com.
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