TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation

Wang, Xiaojia; Gong, Yu; Chen, Zhilong; Gong, Beini; Xie, Ji-Ji; Zhong, Chuan-Qi; Wang, Qilong; Diao, Lianghui; Xu, Anlong; Han, Jiahuai; Altman, Amnon; Li, Yingqiu

doi:10.1038/ni.3259

Cited by 55 publications

(68 citation statements)

References 51 publications

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“…For example, in the immune system FOXP1 is involved in naïve T-cell quiescence 47 and B-cell development 48 . Interestingly, stimulation of T-cell antigen receptor signalling regulates the SUMOylation of the kinase PCKθ 49 and the transcription factor IRF4 50 . This raises the intriguing possibility that TCR signalling in the immune system could be analogous to NMDAR signalling in the nervous system and regulate the SUMOylation of FOXP1 to control its binding to CtBP1 and transcriptional repression.…”

Section: Discussionmentioning

confidence: 99%

SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis

Rocca¹,

Wilkinson²,

Henley³

2017

Sci Rep

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Forkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co-repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly controlled by neuronal activity, in which synapse to nucleus signalling, mediated via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation. Knockdown of FOXP1 in cultured cortical neurons stunts dendritic outgrowth and this phenotype cannot be rescued by replacement with a non-SUMOylatable FOXP1-K670R mutant, indicating that SUMOylation of FOXP1 is essential for regulation of proper neuronal morphogenesis. These results suggest that activity-dependent SUMOylation of FOXP1 may be an important mediator of early cortical development and neuronal network formation in the brain.

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Section: Discussionmentioning

confidence: 99%

SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis

Rocca¹,

Wilkinson²,

Henley³

2017

Sci Rep

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“…According to basic principles of information theory, information is a measure of ordering degree in the system, but the entropy is a measure of disorder degree in the system [18][19]. Information augment means the entropy reduction.…”

Section: Entropy Weightmentioning

confidence: 99%

Research on the assessment indicators for crime prevention lighting in residential areas based on AHP and Entropy Weight

Chen

Zhou

et al. 2016

MATEC Web of Conferences

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Abstract. Lighting can affect the probability of crime. In order to establish safe and secure residential areas' lighting environment, the elements for crime prevention are researched. Originally propose 14 assessment indicators of lighting environment which can be recognized subjectively and may influence crime rate. They are horizontal illuminance illuminance uniformity surround ratio vertical illuminance threedimensional color rendering glare lamp pole height light pole distance lamp aesthetic lamp conciseness color temperature lamp distribution light source. The data came from residents in China. Through screening and giving weights by Analytic Hierarchy Process, there are 7 key assessment indicators left. Then give weights to the ultimate 7 key assessment indicators by Entropy Weight to verify their rank. The results show that 7 key assessment indicators have the same rank in contrast of the two methods. According to the crime prevention influence of the lighting environment, the sort is: vertical illuminance, horizontal illuminance, three-dimensional, color temperature, glare, uniformity of illuminance, color rendering.

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“…Although CD28 is not essential for the recruitment of PKC-θ to the IS, the coalescence of PKC-θ to the c-SMAC is promoted by CD28—requiring its cytoplamic tail and binding to CD80 on the APC [17,53]—and the association of PKC-θ with the actin cytoskeleton via filamin A, a process positively regulated by PKC-θ sumoylation, and by the actin-uncapping protein Rltpr, whose L432P mutant disturbs the localization of PKC-θ but not CD28 in the IS [21,54]; accordingly, we provide evidence that upon TCR engagement, eNOS fosters the recruitment of a fraction of PKC-θ to the actin cytoskeleton. Moreover, eNOS similarly controls the coalescence of PKC-θ and CD28 to the IS, suggesting that an Rltpr-independent mechanism may be involved.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, eNOS similarly controls the coalescence of PKC-θ and CD28 to the IS, suggesting that an Rltpr-independent mechanism may be involved. It is feasible thus that, as part of this mechanism, eNOS-derived NO interfered with the linking of the CD28–filamin A–PKC-θ complex to actin and its flow towards the c-SMAC such as it has been recently described for the desumoylation of PKC-θ, which impairs the coalescence of both PKC-θ and CD28 [21]. Whether the sumoylation of PKC-θ would be also involved in the actin-mediated mechanism by which NO regulates the localization and activation of PKC-θ at the IS remains a standing question.…”

Section: Discussionmentioning

confidence: 99%

eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1

García-Ortiz

Martín-Cófreces

Ibiza³

et al. 2017

PLoS Biol

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The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-θ (PKC-θ) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of β-actin and PKC-θ from the lamellipodium-like distal (d)-SMAC, promoting PKC-θ activation. Furthermore, eNOS-derived NO S-nitrosylated β-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-θ was corroborated by overexpression of PFN1- and actin-binding defective mutants of β-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-θ at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS.

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TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation

Cited by 55 publications

References 51 publications

SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis

SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis

Research on the assessment indicators for crime prevention lighting in residential areas based on AHP and Entropy Weight

eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1

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