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驱动蛋白 Khc-73/KIF13B 通过影响果蝇神经肌肉接头处的内体动力学来调节逆行 BMP 信号。

Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction.

机构信息

Buck Institute for Research on Aging, Novato, CA, United States of America.

Department of Physiology, McGill University, Montreal, QC, Canada.

出版信息

PLoS Genet. 2018 Jan 26;14(1):e1007184. doi: 10.1371/journal.pgen.1007184. eCollection 2018 Jan.

DOI:10.1371/journal.pgen.1007184
PMID:29373576
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5802963/
Abstract

Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons.

摘要

逆行信号对于神经元的生长、功能和存活至关重要；然而，我们对于信号内体如何从突触末端被引导到逆行轴突途径知之甚少。我们已经确定 Khc-73 是一种正向指向的微管运动蛋白，它是果蝇幼虫运动神经元中内体分拣的调节因子。Khc-73 突变体幼虫的突触末梢数量和神经递质释放量正常，但我们发现突触前释放位点的数量显著减少。Khc-73 突变体幼虫的这种缺陷可以通过骨形态发生蛋白 (BMP) 信号的部分遗传缺失或在运动神经元中激活 BMP 信号来增强，反之，BMP 信号的激活通常会增强核内 BMP 转录因子 Mad 的磷酸化形式的积累，也可以通过 Khc-73 的遗传缺失来抑制。通过包括在幼虫运动神经元中的实时成像在内的一系列测定，我们表明 Khc-73 的缺失抑制了逆行结合的内体离开突触区并加入逆行轴突途径的能力。我们的研究结果表明，Khc-73 是突触中内体运输的调节因子，也是运动神经元中逆行 BMP 信号的调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8884/5802963/802c23bbd347/pgen.1007184.g014.jpg
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