DT40 cells lacking the Ca2+-binding protein annexin 5 are resistant to Ca2+-dependent apoptosis.

Proc Natl Acad Sci U S A

Department of Physiology and Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.

Published: June 2002

Annexins are widely expressed Ca(2+)-dependent phospholipid-binding proteins with poorly understood physiological roles. Proposed functions include Ca(2+) channel activity and vesicle trafficking, but neither have been proven in vivo. Here we used targeted gene disruption to generate B-lymphocytes lacking annexin 5 (Anx5) expression and show that this results in reduced susceptibility to a range of apoptotic stimuli. By comparison B-lymphocytes lacking annexin 2 (Anx2) showed no such resistance, providing evidence that this effect is specific to loss of Anx5. The defect in the ANX5(-/-) cells occurs early in the apoptotic program before nuclear condensation, caspase 3 activation, and cell shrinkage, but downstream of an initial Ca(2+) influx. Only UVA/B irradiation induced similar levels of apoptosis in wild-type and ANX5(-/-) cells. Unexpectedly, ANX5(-/-) cells permeabilized in vitro also failed to release mitochondrial cytochrome C, suggesting a possible mechanism for their resistance to apoptosis. These findings demonstrate a role for Anx5 in determining the susceptibility of B-lymphocytes to apoptosis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC123019PMC
http://dx.doi.org/10.1073/pnas.132598099DOI Listing

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