The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis.
The Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation bec...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1797082577436147712 |
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| author | Jones, R Bui, T White, C Madesh, M Krawczyk, C Lindsten, T Hawkins, B Kubek, S Frauwirth, K Wang, Y Conway, S Roderick, H Bootman, MD Shen, H Foskett, J Thompson, C |
| author_facet | Jones, R Bui, T White, C Madesh, M Krawczyk, C Lindsten, T Hawkins, B Kubek, S Frauwirth, K Wang, Y Conway, S Roderick, H Bootman, MD Shen, H Foskett, J Thompson, C |
| author_sort | Jones, R |
| collection | OXFORD |
| description | The Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation because of Ca(2+)-signaling defects. Bax(-/-), Bak(-/-) T cells displayed defective T cell receptor (TCR)- and inositol-1,4,5-trisphosphate (IP(3))-dependent Ca(2+) mobilization because of altered endoplasmic reticulum (ER) Ca(2+) regulation that was reversed by Bax's reintroduction. The ability of TCR-dependent Ca(2+) signals to stimulate mitochondrial NADH production in excess of that utilized for ATP synthesis was dependent on Bax and Bak. Blunting of Ca(2+)-induced mitochondrial NADH elevation in the absence of Bax and Bak resulted in decreased reactive-oxygen-species production, which was required for T cell proliferation. Together, the data establish that Bax and Bak play an essential role in the control of T cell proliferation by modulating ER Ca(2+) release. |
| first_indexed | 2024-03-07T01:29:54Z |
| format | Journal article |
| id | oxford-uuid:933f9095-e989-4c8b-9f2b-5c0a575b2144 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:29:54Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:933f9095-e989-4c8b-9f2b-5c0a575b21442022-03-26T23:31:04ZThe proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:933f9095-e989-4c8b-9f2b-5c0a575b2144EnglishSymplectic Elements at Oxford2007Jones, RBui, TWhite, CMadesh, MKrawczyk, CLindsten, THawkins, BKubek, SFrauwirth, KWang, YConway, SRoderick, HBootman, MDShen, HFoskett, JThompson, CThe Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation because of Ca(2+)-signaling defects. Bax(-/-), Bak(-/-) T cells displayed defective T cell receptor (TCR)- and inositol-1,4,5-trisphosphate (IP(3))-dependent Ca(2+) mobilization because of altered endoplasmic reticulum (ER) Ca(2+) regulation that was reversed by Bax's reintroduction. The ability of TCR-dependent Ca(2+) signals to stimulate mitochondrial NADH production in excess of that utilized for ATP synthesis was dependent on Bax and Bak. Blunting of Ca(2+)-induced mitochondrial NADH elevation in the absence of Bax and Bak resulted in decreased reactive-oxygen-species production, which was required for T cell proliferation. Together, the data establish that Bax and Bak play an essential role in the control of T cell proliferation by modulating ER Ca(2+) release. |
| spellingShingle | Jones, R Bui, T White, C Madesh, M Krawczyk, C Lindsten, T Hawkins, B Kubek, S Frauwirth, K Wang, Y Conway, S Roderick, H Bootman, MD Shen, H Foskett, J Thompson, C The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. |
| title | The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. |
| title_full | The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. |
| title_fullStr | The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. |
| title_full_unstemmed | The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. |
| title_short | The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. |
| title_sort | proapoptotic factors bax and bak regulate t cell proliferation through control of endoplasmic reticulum ca 2 homeostasis |
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