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Calsenilin: A calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment

Nature Medicine volume 4, pages 1177–1181 (1998)Cite this article

Abstract

Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2)1,2,3. Presenilin mutations produce increases in ß-amyloid (Aß) formation and apoptosis in many experimental systems. A cDNA (ALG-3) encoding the last 103 amino acids of PS2 has been identified as a potent inhibitor of apoptosis4,5. Using this PS2 domain in the yeast two-hybrid system, we have identified a neuronal protein that binds calcium and presenilin, which we call calsenilin. Calsenilin interacts with both PS1 and PS2 in cultured cells, and can regulate the levels of a proteolytic product of PS2. Thus, calsenilin may mediate the effects of wild-type and mutant presenilins on apoptosis and on Aß formation. Further characterization of calsenilin may lead to an understanding of the normal role of the presenilins and of the role of the presenilins in Alzheimer disease.

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Figure 1: Molecular characterization of calsenilin.
Figure 2: Co-localization of presenilin and calsenilin.
Figure 3: Association of presenilin and calsenilin in cultured cells.

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Acknowledgements

We thank C. Fredholm for doing 5'-RACE to verify the 5' sequence of calsenilin, K.-N. Liu for preparing and purifying GST–calsenilin, and P. Allen for his excellent advice on the two-hybrid system. This work was supported by grants from the Neuroscience Education and Research Foundation (to J.D.B.), the Alzheimer Association (to J.D.B. and W.W.), the NINDS (to W.W.), and the Korea Research Foundation (E.-K.C.). W.W. is a Pew Scholar.

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Authors and Affiliations

  1. Department of Psychiatry, Mount Sinai School of Medicine One Gustave L. Levy Place, New York, 10029, New York, USA

    Joseph D. Buxbaum, Yuxia Luo & Christina Lilliehook

  2. Department of Neurobiology, Mount Sinai School of Medicine One Gustave L. Levy Place, New York, 10029, New York, USA

    Joseph D. Buxbaum & Christina Lilliehook

  3. Department of Neurology, Genetics and Aging Unit, Massachusetts General Hospital-East, Harvard Medical School, 149 13th Street , Charlestown, Massachusetts, 02129, USA

    Eun-Kyoung Choi, Annette C. Crowley, David E. Merriam & Wilma Wasco

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Correspondence to Joseph D. Buxbaum.

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Buxbaum, J., Choi, EK., Luo, Y. et al. Calsenilin: A calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment. Nat Med 4, 1177–1181 (1998). https://doi.org/10.1038/2673

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