Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse
T cell receptor (TCR) engagement opens Ca2+ release-activated Ca2+ (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the i...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/14850 |
| _version_ | 1811180412122169344 |
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| author | Catherine A Hartzell Katarzyna I Jankowska Janis K Burkhardt Richard S Lewis |
| author_facet | Catherine A Hartzell Katarzyna I Jankowska Janis K Burkhardt Richard S Lewis |
| author_sort | Catherine A Hartzell |
| collection | DOAJ |
| description | T cell receptor (TCR) engagement opens Ca2+ release-activated Ca2+ (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca2+ influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere. Ca2+-dependent retrograde actin flow corrals ER tubule extensions and STIM1/Orai1 complexes to the synapse center, creating a self-organizing process for CRAC channel localization. Our results demonstrate a new role for Ca2+ as a critical regulator of actin organization and dynamics at the synapse, and reveal potential feedback loops through which Ca2+ influx may modulate TCR signaling. |
| first_indexed | 2024-04-11T09:02:43Z |
| format | Article |
| id | doaj.art-5dd68499391f412b8f89333305f092c1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:02:43Z |
| publishDate | 2016-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5dd68499391f412b8f89333305f092c12022-12-22T04:32:43ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.14850Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapseCatherine A Hartzell0Katarzyna I Jankowska1Janis K Burkhardt2Richard S Lewis3https://orcid.org/0000-0002-6010-7403Immunology Program, Stanford University, Stanford, United States; Department of Molecular and Cellular Physiology, Stanford University, Stanford, United StatesDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, United States; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, United States; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesImmunology Program, Stanford University, Stanford, United States; Department of Molecular and Cellular Physiology, Stanford University, Stanford, United StatesT cell receptor (TCR) engagement opens Ca2+ release-activated Ca2+ (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca2+ influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere. Ca2+-dependent retrograde actin flow corrals ER tubule extensions and STIM1/Orai1 complexes to the synapse center, creating a self-organizing process for CRAC channel localization. Our results demonstrate a new role for Ca2+ as a critical regulator of actin organization and dynamics at the synapse, and reveal potential feedback loops through which Ca2+ influx may modulate TCR signaling.https://elifesciences.org/articles/14850immunological synapseendoplasmic reticulumT lymphocyteactin dynamicscalcium release-activated calcium (CRAC) channelscalcium |
| spellingShingle | Catherine A Hartzell Katarzyna I Jankowska Janis K Burkhardt Richard S Lewis Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse eLife immunological synapse endoplasmic reticulum T lymphocyte actin dynamics calcium release-activated calcium (CRAC) channels calcium |
| title | Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse |
| title_full | Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse |
| title_fullStr | Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse |
| title_full_unstemmed | Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse |
| title_short | Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse |
| title_sort | calcium influx through crac channels controls actin organization and dynamics at the immune synapse |
| topic | immunological synapse endoplasmic reticulum T lymphocyte actin dynamics calcium release-activated calcium (CRAC) channels calcium |
| url | https://elifesciences.org/articles/14850 |
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