Chen Chun-Kan, Bregere Catherine, Paluch Jeremy, Lu Jason F, Dickman Dion K, Chang Karen T
1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA [2] Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA [2].
Nat Commun. 2014 Jun 30;5:4246. doi: 10.1038/ncomms5246.
Phosphorylation has emerged as a crucial regulatory mechanism in the nervous system to integrate the dynamic signalling required for proper synaptic development, function and plasticity, particularly during changes in neuronal activity. Here we present evidence that Minibrain (Mnb; also known as Dyrk1A), a serine/threonine kinase implicated in autism spectrum disorder and Down syndrome, is required presynaptically for normal synaptic growth and rapid synaptic vesicle endocytosis at the Drosophila neuromuscular junction (NMJ). We find that Mnb-dependent phosphorylation of Synaptojanin (Synj) is required, in vivo, for complex endocytic protein interactions and to enhance Synj activity. Neuronal stimulation drives Mnb mobilization to endocytic zones and triggers Mnb-dependent phosphorylation of Synj. Our data identify Mnb as a synaptic kinase that promotes efficient synaptic vesicle recycling by dynamically calibrating Synj function at the Drosophila NMJ, and in turn endocytic capacity, to adapt to conditions of high synaptic activity.
磷酸化已成为神经系统中一种关键的调节机制，用于整合正常突触发育、功能和可塑性所需的动态信号，尤其是在神经元活动变化期间。在这里，我们提供证据表明，小头畸形（Mnb；也称为Dyrk1A），一种与自闭症谱系障碍和唐氏综合征有关的丝氨酸/苏氨酸激酶，在果蝇神经肌肉接头（NMJ）处，对于正常的突触生长和快速的突触小泡内吞作用是突触前必需的。我们发现，在体内，Synaptojanin（Synj）的Mnb依赖性磷酸化对于复杂的内吞蛋白相互作用和增强Synj活性是必需的。神经元刺激促使Mnb向内吞区域移动，并触发Synj的Mnb依赖性磷酸化。我们的数据确定Mnb是一种突触激酶，它通过在果蝇NMJ处动态校准Synj功能，进而校准内吞能力，以适应高突触活动条件，从而促进有效的突触小泡循环利用。
