Matefin/SUN-1 is a nuclear envelope receptor for CED-4 during Caenorhabditis elegans apoptosis
- Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel
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Edited by Roger D. Kornberg, Stanford University School of Medicine, Stanford, CA, and approved July 18, 2006 (received for review May 22, 2006)
Abstract
In Caenorhabditis elegans, the antiapoptotic protein CED-9 is localized at the mitochondria, where it binds the proapoptotic protein CED-4. Induction of apoptosis begins when the proapoptotic protein EGL-1 is expressed and binds CED-9. The binding of EGL-1 to CED-9 releases CED-4 from CED-9 and causes the activation of the caspase CED-3. Upon its release from CED-9, CED-4 rapidly translocates to the nuclear envelope (NE) in a CED-3-independent manner. However, the identity of the NE receptor for CED-4 and its possible role in the execution of apoptosis has remained unknown. Here, we show that the inner nuclear membrane SUN-domain protein matefin/SUN-1 is the NE receptor for CED-4. Our data demonstrate that matefin/SUN-1 binds CED-4 and is specifically required for CED-4 translocation and maintenance at the NE. The role of matefin/SUN-1 in the execution of apoptosis is further suggested by the significant reduction in the number of apoptotic cells in the organism after matefin/SUN-1 down-regulation by RNAi. The finding that matefin/SUN-1 is required for the execution of apoptosis adds an important link between cytoplasmic and nuclear apoptotic events.
Footnotes
- *To whom correspondence should be addressed. E-mail: gru{at}vms.huji.ac.il
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Author contributions: Y.G. designed research; Y.B.T., A.M., and N.M.-B. performed research; A.M. contributed new reagents/analytic tools; Y.B.T. and Y.G. analyzed data; and Y.G. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviation:
- NE,
- nuclear envelope.
- © 2006 by The National Academy of Sciences of the USA
