RESUMEN
Actin dynamics control early T-cell receptor (TCR) signalling during T-cell activation. However, the precise regulation of initial actin rearrangements is not completely understood. Here, we have investigated the regulatory role of the phosphatase Slingshot-1 (SSH1) in this process. Our data show that SSH1 rapidly polarises to nascent cognate synaptic contacts and later relocalises to peripheral F-actin networks organised at the mature immunological synapse. Knockdown of SSH1 expression by CRISPR/Cas9-mediated genome editing or small interfering RNA reveal a regulatory role for SSH1 in CD3ε conformational change, allowing Nck binding and proper downstream signalling and immunological synapse organisation. TCR triggering induces SSH1-mediated activation of actin dynamics through a mechanism mediated by Limk-1 inactivation. These data suggest that during early TCR activation, SSH1 is required for rapid F-actin rearrangements that mediate initial conformational changes of the TCR, integrin organisation and proximal signalling events for proper synapse organisation. Therefore, the SSH1 and Limk-1 axis is a key regulatory element for full T cell activation.
Asunto(s)
Quinasas Lim , Fosfoproteínas Fosfatasas , Receptores de Antígenos de Linfocitos T , Humanos , Quinasas Lim/metabolismo , Quinasas Lim/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/genética , Actinas/metabolismo , Actinas/genética , Activación de Linfocitos , Células Jurkat , Linfocitos T/metabolismo , Linfocitos T/inmunología , Transducción de Señal , Sinapsis Inmunológicas/metabolismoRESUMEN
BACKGROUND: We conducted research to investigate the effects of the eruption sequence of posterior teeth, arch dimensions, and incisor inclination on dental crowding. MATERIAL AND METHODS: A cross-sectional analytic study was performed on 100 patients (54 boys and 46 girls; mean ages: 11.69 and 11.16 years, respectively). Seq1 (canine-3-/second premolar-5-) or Seq2 (5/3) eruption sequences were recorded in maxilla, and Seq3 (canine-3-/first premolar-4-) or Seq4 (4/3) eruption sequences in mandible; tooth size, available space, tooth size-arch length discrepancy (TS-ALD), arch lengths, incisor inclination and distance, and skeletal relationship were noted. RESULTS: The most common eruption sequences in the maxilla and mandible were Seq1 (50.6%), and Seq3 (52.1%), respectively. In the maxilla, posterior tooth sizes were larger in crowded cases. In the mandible, anterior and posterior tooth sizes were larger in crowded patients. No relationship between incisor variables and the maxillo-mandibular relationship and dental crowding was found. A negative correlation between inferior TS-ALD and the mandibular plane was found. CONCLUSIONS: Seq1 and Seq 2 in the maxilla and Seq 3 and Seq 4 in the mandible were equally prevalent. An eruption sequence of 3-5 in the maxilla and 3-4 in the mandible is more likely to cause crowding.