Lipid raft-associated stomatin enhances cell fusion.
Membrane fusions that occur during vesicle transport, virus infection, and tissue development, involve receptors that mediate membrane contact and initiate fusion and effectors that execute membrane reorganization and fusion pore formation. Some of these fusogenic receptors/effectors are preferentially recruited to lipid raft membrane microdomains. Therefore, major constituents of lipid rafts, such as stomatin, may be involved in the regulation of cell-cell fusion. Stomatin produced in cells can be released to the extracellular environment, either through protein refolding to pass across lipid bilayer or through exosome trafficking. We report that cells expressing more stomatin or exposed to exogenous stomatin are more prone to undergoing cell fusion. During osteoclastogenesis, depletion of stomatin inhibited cell fusion but had little effect on tartrate-resistant acid phosphatase production. Moreover, in stomatin transgenic mice, increased cell fusion leading to enhanced bone resorption and subsequent osteoporosis were observed. With its unique molecular topology, stomatin forms molecular assembly within lipid rafts or on the appositional plasma membranes, and promotes membrane fusion by modulating fusogenic protein engagement.-Lee, J.-H., Hsieh, C.-F., Liu, H.-W., Chen, C.-Y., Wu, S.-C., Chen, T.-W., Hsu, C.-S., Liao, Y.-H., Yang, C.-Y., Shyu, J.-F., Fischer, W. B., Lin, C.-H. Lipid raft-associated stomatin enhances cell fusion.
Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Microbiology and Immunology.|Institute of Biochemistry and Molecular Biology.
Jui-Hao
JH
Lee
Institute of Microbiology and Immunology.
Chia-Fen
CF
Hsieh
Institute of Microbiology and Immunology.|Chong Hin Loon Memorial Cancer and Biotherapy Research Center, and.
Hong-Wen
HW
Liu
Institute of Microbiology and Immunology.|Department of Surgery, I-Lan, Taiwan.
Chin-Yau
CY
Chen
Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
Shao-Chin
SC
Wu
Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
Tung-Wei
TW
Chen
Institute of Microbiology and Immunology.
Chih-Sin
CS
Hsu
Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
Yu-Hsiu
YH
Liao
Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; and.
Chih-Yung
CY
Yang
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
Jia-Fwu
JF
Shyu
Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
Wolfgang B
WB
Fischer
Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan; linch@ym.edu.tw.|Institute of Microbiology and Immunology.|Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
Chi-Hung
CH
Lin
D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D021962:Membrane Microdomains / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis
D008565:Membrane Proteins; C036860:STOM protein, human
exosome; membrane permeability; osteoclastogenesis