Wolfstetter G, Masudi T, Uçkun E, Zhu J Y, Yi M, Anthonydhason V, Guan J, Sonnenberg H, Han Z, Palmer R H
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, 41390, Gothenburg, Sweden.
Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Cell Commun Signal. 2025 May 17;23(1):229. doi: 10.1186/s12964-025-02150-x.
Anaplastic lymphoma kinase (Alk) signaling is important in a variety of biological contexts such as cell type specification, regulation of metabolic and endocrine programs, behavior, and cancer. In this work, we generated a Tango GPCR assay-based, dimerization-sensitive Alk activity reporter (Alk) and followed receptor activation throughout Drosophila development. Alk reports Alk activation in embryonic and larval tissues previously linked to Alk signaling. Remarkably, Alk was active in the heart of Drosophila larvae and adult flies. We show that cardiomyocytes express Alk from late embryonic stages to adulthood, while jeb expression in pericardial cells coincided with Alk activity. Perturbation of cardiac Alk signaling leads to decreased adult survival as well as lower fitness and increased lethality in response to heat stress. In keeping with a role for Alk, heart measurements reveal arrythmia and irregular muscle contraction upon ligand stimulation. Finally, activation of cardiac Alk signaling induces hyperplasia in the accessory wing hearts of adult flies.
间变性淋巴瘤激酶（Alk）信号传导在多种生物学背景中都很重要，例如细胞类型特化、代谢和内分泌程序的调节、行为以及癌症。在这项研究中，我们基于Tango GPCR检测法生成了一种对二聚化敏感的Alk活性报告基因（Alk），并在果蝇发育过程中追踪受体激活情况。Alk报告了先前与Alk信号传导相关的胚胎和幼虫组织中的Alk激活。值得注意的是，Alk在果蝇幼虫和成年果蝇的心脏中具有活性。我们发现心肌细胞从胚胎后期到成年期都表达Alk，而心包细胞中的jeb表达与Alk活性一致。心脏Alk信号传导的扰动会导致成年果蝇存活率降低，以及在热应激下适应性降低和致死率增加。与Alk的作用一致，心脏测量显示在配体刺激下会出现心律失常和肌肉收缩不规则。最后，心脏Alk信号传导的激活会诱导成年果蝇副翼心脏中的细胞增生。
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