Abnormal larval neuromuscular junction morphology and physiology in Drosophila prickle isoform mutants with known axonal transport defects and adult seizure behavior.

IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Journal of neurogenetics Pub Date : 2022-03-01 DOI:10.1080/01677063.2022.2093353
Atsushi Ueda, Tristan C D G O'Harrow, Xiaomin Xing, Salleh Ehaideb, J Robert Manak, Chun-Fang Wu
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Abstract

Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pksple flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.

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棘果蝇异型突变体的异常幼体神经肌肉连接形态和生理,已知轴突运输缺陷和成年癫痫行为。
先前的研究表明,果蝇平面细胞极性基因prickle (pk)对幼虫运动轴突微管介导的囊泡运输和与神经元回路高兴奋性相关的成人癫痫行为具有显著的突变作用。刺-刺(pkpk)和刺-刺-腿(pksple)同型突变等位基因(以下分别称为pk和单等位基因)表现出不同的表型。虽然pk和simple都影响幼虫的运动轴突运输,但只有simple会导致运动回路和行为亢奋。然而,在异等位基因pkpk/ pkple果蝇中,两种同工异构体的突变明显抵消了成年运动回路和行为过度兴奋性的改善。我们进一步研究了轴突运输改变对幼虫神经肌肉连接(NMJ)发育和功能的影响。我们发现pk等位基因和单一等位基因都存在强大的显性表型,包括突触末端过度生长(通过抗hrp和-Dlg免疫染色显示)和囊泡释放同步性差(通过突触扣点记录显示)。然而,我们仅在pk/pk幼虫中观察到突触传递的隐性改变,即pk/pk中兴奋性连接电位(EJP)振幅增加,而pk/+或单/单中没有。有趣的是,对于由突触前Ca2+通道维持的运动终端兴奋性,pk和simple都发挥了强大的作用,产生了延长的去极化。值得注意的是,只有sple起主导作用,而pk/+表现正常,但能够抑制sple表型,即pk/sple表现正常。我们的观察对比了pk和简单同种异构体的不同作用,并强调了它们在幼虫NMJ的各种结构和功能方面的不同,可变的表型表达。
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来源期刊
Journal of neurogenetics
Journal of neurogenetics 医学-神经科学
CiteScore
4.40
自引率
0.00%
发文量
13
审稿时长
>12 weeks
期刊介绍: The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms
期刊最新文献
The initial years of the Cold Spring Harbor Laboratory summer course on the neurobiology of Drosophila. Clinical potential of epigenetic and microRNA biomarkers in PTSD. Molecular analysis of SMN2, NAIP, and GTF2H2 gene deletions and relationships with clinical subtypes of spinal muscular atrophy. Neurobiology of egg-laying behavior in Drosophila: neural control of the female reproductive system. Memoir of the early years of the CSHL summer Drosophila neurobiology course: 1984-1985.
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