The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence
- Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom
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Edited by Matthew D. Scharff, Albert Einstein College of Medicine, Bronx, NY, and approved February 25, 2009 (received for review October 28, 2008)
Abstract
The carboxyterminal region of activation-induced deaminase (AID) is required for its function in Ig class switch recombination (CSR) and also contains a nuclear-export sequence (NES). Here, based on an extensive fine-structure mutation analysis of the AID NES, as well as from AID chimeras bearing heterologous NESs, we show that while a functional NES is indeed essential for CSR, it is not sufficient. The precise nature of the NES is critical both for AID stabilization and CSR function: minor changes in the NES can perturb stabilization and CSR without jeopardizing nuclear export. The results indicate that the AID NES fulfills a function beyond simply providing a signal for nuclear export and suggest the possibility that the quality of exportin-binding may be critical to the stabilization of AID and its activity in CSR.
- activation-induced deaminase
- antibody diversification
- immunoglobulin class switching
- exportin
- nuclear transport
Footnotes
- 1To whom correspondence should be addressed. E-mail: msn{at}mrc-lmb.cam.ac.uk
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Author contributions: R.G., C.R., and M.S.N. designed research; R.G. and C.R. performed research; R.G., C.R., and M.S.N. analyzed data; and M.S.N. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0810808106/DCSupplemental.
