A PDZ-RapGEF promotes synaptic development in Caenorhabditis elegans through a Rap/Rac signaling pathway.

IF 3.6 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2025-08-15 Epub Date: 2025-08-26 DOI:10.1242/dev.204678
Reagan Lamb, Michael Scales, Julie Watkins, Martin Werner, Salvatore J Cherra
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引用次数: 0

Abstract

Small G proteins coordinate the development of nerve terminals. The activity of G proteins is finely tuned by GTPase regulatory proteins. Previously, we have observed that PXF-1, a Caenorhabditis elegans GTPase regulatory protein, is required for the function of cholinergic motor neurons. Here, we investigated how PXF-1 coordinates the development of presynaptic terminals at the molecular level. We observed that PXF-1 acts through RAP-1 to promote synapse development. Subsequently, we found that pxf-1 mutants display a reduction in RAC-2 activity, which is required for cholinergic synapse development. We observed that RAC-2 acts downstream of RAP-1. Finally, we identified a physical interaction between RAP-1 and TIAM-1, a Rac guanine exchange factor, which links PXF-1 function to the presynaptic actin cytoskeleton through RAC-2 activation. These findings highlight how small G protein signaling pathways interact to coordinate the development of presynaptic terminals.

PDZ-RapGEF通过Rap/Rac信号通路促进线虫突触发育。
小G蛋白协调神经末梢的发育。G蛋白的活性由GTPase调节蛋白精细调节。先前,我们观察到秀丽隐杆线虫GTPase调节蛋白PXF-1是胆碱能运动神经元功能所必需的。在这里,我们研究了PXF-1如何在分子水平上协调突触前终末的发育。我们观察到PXF-1通过RAP-1促进突触发育。随后,我们发现pxf-1突变体显示出胆碱能突触发育所需的RAC-2活性降低。我们观察到RAC-2作用于RAP-1的下游。最后,我们确定了RAP-1和Rac鸟嘌呤交换因子TIAM-1之间的物理相互作用,该相互作用通过Rac -2激活将PXF-1功能与突触前肌动蛋白细胞骨架联系起来。这些发现强调了小G蛋白信号通路如何相互作用以协调突触前末端的发育。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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