@article{2dfef890104b4fbd8291adf28b076620,
title = "The inositol 5-phosphatase INPP5B regulates B cell receptor clustering and signaling",
abstract = "Upon antigen binding, the B cell receptor (BCR) undergoes clustering to form a signalosome that propagates downstream signaling required for normal B cell development and physiology. BCR clustering is dependent on remodeling of the cortical actin network, but the mechanisms that regulate actin remodeling in this context remain poorly defined. In this study, we identify the inositol 5-phosphatase INPP5B as a key regulator of actin remodeling, BCR clustering, and downstream signaling in antigen-stimulated B cells. INPP5B acts via dephosphorylation of the inositol lipid PI(4,5)P2 that in turn is necessary for actin disassembly, BCR mobilization, and cell spreading on immobilized surface antigen. These effects can be explained by increased actin severing by cofilin and loss of actin linking to the plasma membrane by ezrin, both of which are sensitive to INPP5B-dependent PI(4,5)P2 hydrolysis. INPP5B is therefore a new player in BCR signaling and may represent an attractive target for treatment of B cell malignancies caused by aberrant BCR signaling.",
author = "Alaa Droubi and Connor Wallis and Anderson, {Karen E} and Saifur Rahman and {de Sa}, Aloka and Taufiq Rahman and Stephens, {Len R} and Hawkins, {Philip T} and Martin Lowe",
note = "Funding Information: and a Manchester-Singapore A*Star PhD studentship, respectively. K.E. Anderson, L.R. Stephens, and P.T. Hawkins were supported by a BBSRC research grant (BB/PO13384/1). S. Rah-man was funded by a PhD studentship from Cambridge Trust. The authors declare no competing financial interests. Funding Information: A. Droubi was supported by a BBSRC research grant (BB/ S014799/1) awarded to M. Lowe. C. Wallis and A.D. Sa were supported by a Wellcome Trust PhD studentship (222757/Z/21/Z) Funding Information: We are grateful to Peter March at the Faculty of Biology, Medicine and Health (FBMH) bioimaging facility and to Gareth Howell and David Chapmen at the FBMH flow cytometry facility for their help and advice. We thank Robin F. Irvine (retired, University of Cambridge, Cambridge, UK) for the generous gifts of plasmids, and the electroporation equipment. We also thank Gloria Lopez-Castejon and Rodrigo Diaz Pino (University of Manchester, Manchester, UK) for kindly providing PBMCs. A. Droubi was supported by a BBSRC research grant (BB/ S014799/1) awarded to M. Lowe. C. Wallis and A.D. Sa were supported by a Wellcome Trust PhD studentship (222757/Z/21/Z) and a Manchester-Singapore A*Star PhD studentship, respectively. K.E. Anderson, L.R. Stephens, and P.T. Hawkins were supported by a BBSRC research grant (BB/PO13384/1). S. Rahman was funded by a PhD studentship from Cambridge Trust. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2022 Droubi et al.",
year = "2022",
month = sep,
day = "5",
doi = "10.1083/jcb.202112018",
language = "English",
volume = "221",
journal = "The Journal of cell biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "9",
}