Opposing roles for RhoH GTPase during T-cell migration and activation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Opposing roles for RhoH GTPase during T-cell migration and activation. / Baker, Christina M; Comrie, William A; Hyun, Young-Min; Chung, Hung-Li; Fedorchuk, Christine A; Lim, Kihong; Brakebusch, Cord; McGrath, James L; Waugh, Richard E; Meier-Schellersheim, Martin; Kim, Minsoo.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 109, Nr. 26, 26.06.2012, s. 10474-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Opposing roles for RhoH GTPase during T-cell migration and activation
AU - Baker, Christina M
AU - Comrie, William A
AU - Hyun, Young-Min
AU - Chung, Hung-Li
AU - Fedorchuk, Christine A
AU - Lim, Kihong
AU - Brakebusch, Cord
AU - McGrath, James L
AU - Waugh, Richard E
AU - Meier-Schellersheim, Martin
AU - Kim, Minsoo
PY - 2012/6/26
Y1 - 2012/6/26
N2 - T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients ("go" signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition ("stop" signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1-GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1-GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4(+) T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals.
AB - T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients ("go" signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition ("stop" signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1-GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1-GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4(+) T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals.
U2 - 10.1073/pnas.1114214109
DO - 10.1073/pnas.1114214109
M3 - Journal article
C2 - 22689994
VL - 109
SP - 10474
EP - 10479
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -
ID: 40299618