Published 11 March 2002. doi:10.1084/jem.20011758
© Rockefeller University Press, 0022-1007/2002/3/673/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 6, March 18, 2002 673-681
Transient Receptor Potential 1 Regulates Capacitative Ca2+ Entry and Ca2+ Release from Endoplasmic Reticulum in B Lymphocytes
Yasuo Mori1,
Minoru Wakamori1,
Tomoya Miyakawa2,
Meredith Hermosura3,
Yuji Hara1,
Motohiro Nishida1,
Kenzo Hirose2,
Akiko Mizushima2,
Mari Kurosaki4,
Emiko Mori1,
Kumiko Gotoh4,
Takaharu Okada1,
Andrea Fleig3,
Reinhold Penner3,
Masamitsu Iino2 and
Tomohiro Kurosaki4
1 Center for Integrative Bioscience and Department of Information Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
2 Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, CREST, Japan Science and Technology Corporation, Tokyo 113-0033, Japan
3 Laboratory of Cell and Molecular Signaling, Center for Biomedical Research at The Queen's Medical Center, and John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI 96813
4 Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, and Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Moriguchi 570-8506, Japan
Address correspondence to Yasuo Mori, Center for Integrative Bioscience, National Institute for Physiological Sciences, Myodaiji-cho, Okazaki 444-8585, Japan. Phone: 81-564-55-7722; Fax: 81-564-55-7721; E-mail: moriy{at}nips.ac.jp or Tomohiro Kurosaki, Dept. of Molecular Genetics, Institute for Liver Research, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi 570-8506, Japan. Phone: 81-6-6993-9445; Fax: 81-6-6994-6099; E-mail: kurosaki{at}mesh.ne.jp
Capacitative Ca2+ entry (CCE) activated by release/depletion of Ca2+ from internal stores represents a major Ca2+ influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca2+ release-activated Ca2+ currents and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptormediated Ca2+ oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP3 receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca2+ signaling in B lymphocytes.
Key Words: B cell receptor capacitative Ca2+ entry store-operated Ca2+ channel Ca2+ release TRP

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