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果蝇细丝蛋白 Jitterbug(Jbug)异构体在发育过程中的特异性作用。

Isoform-specific roles of the Drosophila filamin-type protein Jitterbug (Jbug) during development.

机构信息

Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

出版信息

Genetics. 2021 Oct 2;219(2). doi: 10.1093/genetics/iyab100.

Abstract

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.

摘要

细丝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。作为多功能信号支架的关键组成部分,细丝蛋白与发育异常和癌症有关。存在多种细丝蛋白同工型,这使得每种同工型在发育和疾病过程中可能具有不同的功能。在这里,我们对编码果蝇中两种细丝蛋白之一的 jitterbug(jbug)进行了初步表征。我们生成了 Jbug 抗血清,该抗血清可识别所有剪接形式,并在发育过程中显示出不同 Jbug 同工型的差异表达,以及 Jbug 蛋白的大量母体贡献。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 null 等位基因、仅影响一部分的 hypomorphic 等位基因,以及用于 Gal4 驱动主要同工型表达的 UAS 线。使用这些工具,我们证明 Jbug 对于生存是必需的,并且特定的同工型对于包括成年胸刺和胚胎腹齿在内的富含肌动蛋白的突起的形成是必需的。我们还表明,Jbug 的特定同工型在表皮内的定位存在差异,并且母源和合子缺失 jbug 会破坏几个上皮细胞类型中的 Crumbs(Crb)定位。

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