Sukhanova Tatiana, Renkemeyer M Katie, Pritchett Nicholas, Berke Brett, Keshishian Haig
Molecular, Cellular, and Developmental Biology Department, Yale University, New Haven, Connecticut, USA.
Department of Agricultural and Biological Sciences, Truman State University, Kirksville, Missouri, USA.
Dev Neurobiol. 2025 Jul;85(3):e22988. doi: 10.1002/dneu.22988.
Numb is an adaptor protein with functions that include the endocytic processing of activated growth factor receptors. As growth factor signaling contributes to the development and function of the Drosophila neuromuscular junction (NMJ), we examined whether Numb is present at the larval NMJ and whether it is required for the growth, physiology, and/or plasticity of this synapse. Antisera prepared against Numb protein labeled NMJ presynaptic boutons, and RNAi knockdown of Numb, when directed to the presynaptic side, reduced the size of the NMJ. This was accompanied by smaller excitatory junctional potentials with reduced synaptic quantal content. Numb loss of function also suppressed the activity-dependent expansion of the NMJ, suggesting a requirement for Numb in synaptic growth plasticity. Similar phenotypes have been described at the NMJ for mutations of the Type II BMP growth factor receptor gene wishful thinking (wit). As Numb is known to participate in growth factor receptor signaling in other systems, we tested whether a genetic interaction exists between the numb and wit genes. We observed a reduction of NMJ size in double heterozygotes compared to the single heterozygote control, suggesting that Numb is a candidate for processing growth factor signals during synaptic development and plasticity at the larval NMJ.
Numb是一种衔接蛋白，其功能包括对活化生长因子受体进行内吞处理。由于生长因子信号传导有助于果蝇神经肌肉接头（NMJ）的发育和功能，我们研究了Numb是否存在于幼虫的NMJ处，以及它是否是该突触生长、生理功能和/或可塑性所必需的。针对Numb蛋白制备的抗血清标记了NMJ的突触前终扣，并且当将Numb的RNA干扰作用于突触前侧时，会减小NMJ的大小。这伴随着较小的兴奋性接头电位以及突触量子含量的降低。Numb功能丧失还抑制了NMJ的活动依赖性扩张，表明Numb在突触生长可塑性中是必需的。在NMJ处，已描述了II型BMP生长因子受体基因“如意算盘”（wit）突变的类似表型。由于已知Numb在其他系统中参与生长因子受体信号传导，我们测试了numb和wit基因之间是否存在遗传相互作用。与单杂合子对照相比，我们观察到双杂合子中NMJ大小减小，这表明Numb是在幼虫NMJ的突触发育和可塑性过程中处理生长因子信号的一个候选因素。
