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Isoform-specific roles of the Drosophila filamin-type protein Jitterbug (Jbug) during development
bioRxiv - Developmental Biology Pub Date : 2021-05-12 , DOI: 10.1101/2020.10.13.337626
SeYeon Chung , Thao Phuong Le , Vishakha Vishwakarma , Yim Ling Cheng , Deborah J. Andrew

Filamins are highly conserved actin-crosslinking proteins that regulate organization of the actin cytoskeleton. As key components of versatile signaling scaffolds, filamins are implicated in developmental anomalies and cancer. Multiple isoforms of filamins exist, raising the possibility of distinct functions for each isoform during development and in disease. Here, we provide an initial characterization of jitterbug (jbug), which encodes one of the two filamin-type proteins in Drosophila. We generate Jbug antiserum that recognizes all of the spliced forms and reveals differential expression of different Jbug isoforms during development, and a significant maternal contribution of Jbug protein. To reveal the function of Jbug isoforms, we create new genetic tools, including a null allele that deletes all isoforms, hypomorphic alleles that affect only a subset, and UAS lines for Gal4-driven expression of the major isoforms. Using these tools, we demonstrate that Jbug is required for viability and that specific isoforms are required in the formation of actin-rich protrusions including thoracic bristles in adults and ventral denticles in the embryo. We also show that specific isoforms of Jbug show differential localization within epithelia and that maternal and zygotic loss of jbug disrupts Crumbs (Crb) localization in several epithelial cell types.

中文翻译:

果蝇丝状蛋白Jitterbug(Jbug)在发育过程中的同工型特定作用。

纤维蛋白是高度保守的肌动蛋白交联蛋白,可调节肌动蛋白细胞骨架的组织。作为多功能信号转导支架的关键组成部分,纤维蛋白与发育异常和癌症有关。纤维蛋白存在多种同工型,从而增加了在发育中和疾病中每种同工型具有不同功能的可能性。在这里,我们提供了jitterbug(jbug)的初始特征,它编码了果蝇中两个丝素蛋白类型蛋白之一。我们生成识别所有剪接形式的Jbug抗血清,并揭示发育过程中不同Jbug亚型的差异表达,以及Jbug蛋白的重要母体贡献。为了揭示Jbug同工型的功能,我们创建了新的遗传工具,包括删除所有同工型的无效等位基因,仅影响一个亚型的亚等位基因,以及用于主要异构体的Gal4驱动表达的UAS品系。使用这些工具,我们证明了Jbug是生存力所必需的,并且在形成富含肌动蛋白的突起(包括成人中的胸毛和胚胎的腹侧齿状体)时,需要特定的同工型。我们还显示,Jbug的特定同工型显示上皮细胞内的差异化定位,并且jbug的母体和合子损失破坏了几种上皮细胞类型中的Crumbs(Crb)定位。
更新日期:2021-05-13
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