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max in WT synaptoneurosomes, suggesting that Src signaling can be downregulated in KI synapses. Conversely, our power to rescue SERT perform in KI midbrain synaptoneurosomes through the inhibition of FAK indicates elevated FAK signaling downstream from the Pro32Pro33 mutant, as confirmed by greater pFAK localization in 5-HT synapses. Our knowledge hence advise the Src–FAK pathway is uncoupled by constitutive activation of integrin β3, and thus Every kinase may very well be influencing SERT independently.
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The context-dependent character of SERT regulation is underscored through the lack of colocalization of SERT with focal adhesion proteins in KI synapses. This indicates that the Affiliation of SERT with integrin signaling complexes will not be necessary for the regulation of your transporter by constitutive signaling downstream on the “primed” Pro32Pro33 mutant.
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