Nakhost Arash, Houeland Gry, Castellucci Vincent F, Sossin Wayne S
Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
J Neurosci. 2003 Jul 16;23(15):6238-44. doi: 10.1523/JNEUROSCI.23-15-06238.2003.
We discovered a novel alternatively spliced form of synaptotagmin I (Syt I). This splicing event is conserved over evolution and, in Aplysia, results in a two amino acid insert in the juxtamembrane domain of Syt I (Syt IVQ). Both Syt I and Syt IVQ are localized to synaptic vesicles; however, we also observed punctae that contained one or the other spliced products. Both Syt I and Syt IVQ are phosphorylated at the adjacent PKC site. Overexpression of Syt IVQ, but not of Syt I, in Aplysia neurons blocked the ability of serotonin to reverse synaptic depression. This effect is upstream of PKC activation, because neither Syt IVQ nor Syt I blocked the effects of phorbol esters on reversing synaptic depression or the effects of serotonin on facilitating nondepressed synapses. Our results demonstrate a physiological role for splicing in the juxtamembrane domain of Syt I.
我们发现了一种新的突触结合蛋白I（Syt I）可变剪接形式。这种剪接事件在进化过程中是保守的，在海兔中，它导致Syt I（Syt IVQ）的近膜结构域中插入两个氨基酸。Syt I和Syt IVQ都定位于突触小泡；然而，我们也观察到含有其中一种剪接产物的点状结构。Syt I和Syt IVQ在相邻的蛋白激酶C（PKC）位点均被磷酸化。在海兔神经元中过表达Syt IVQ而非Syt I，会阻断5-羟色胺逆转突触抑制的能力。这种效应发生在PKC激活的上游，因为Syt IVQ和Syt I均未阻断佛波酯对逆转突触抑制的作用或5-羟色胺对促进未受抑制突触的作用。我们的结果证明了Syt I近膜结构域剪接的生理作用。
