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AlkTango reveals a role for Jeb/Alk signaling in the Drosophila heart

G Wolfstetter1, T Masudi2, E Uçkun2

  • 1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, 41390, Gothenburg, Sweden. georg.wolfstetter@su.se.

Cell Communication and Signaling : CCS
|May 17, 2025
PubMed

Insights

Anaplastic lymphoma kinase (Alk) signaling is crucial for heart function in Drosophila. This study reveals Alk activity in cardiomyocytes, impacting survival, fitness, and heart rhythm.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Cardiovascular Physiology

Background:

  • Anaplastic lymphoma kinase (Alk) signaling plays a vital role in numerous biological processes, including cell development, metabolic regulation, and cancer.
  • Understanding Alk signaling dynamics during development is crucial for deciphering its multifaceted roles.

Purpose of the Study:

  • To develop and utilize a novel reporter system to track Anaplastic lymphoma kinase (Alk) activity throughout Drosophila development.
  • To investigate the previously uncharacterized role of Alk signaling in the Drosophila heart.

Main Methods:

  • Generation of a dimerization-sensitive Alk activity reporter (AlkTango) based on the Tango GPCR assay.
  • Monitoring AlkTango activity across various embryonic and larval tissues.
  • Analysis of cardiac function, survival rates, and stress responses in Drosophila with perturbed cardiac Alk signaling.

Main Results:

  • AlkTango reporter successfully mapped Alk activation in known embryonic and larval tissues.
  • Remarkably, AlkTango activity was detected in the larval and adult Drosophila heart.
  • Perturbation of cardiac Alk signaling resulted in reduced adult survival, decreased fitness, heat stress sensitivity, cardiac arrhythmias, and accessory heart hyperplasia.

Conclusions:

  • Anaplastic lymphoma kinase (Alk) signaling is active and functionally important in the Drosophila heart from embryonic stages to adulthood.
  • Cardiac Alk signaling influences heart function, organismal fitness, and survival, particularly under stress.
  • This study highlights a novel role for Alk in cardiovascular physiology and development.
Keywords:
CRISPR/Cas9Cardiac arrythmiaCardiomyocyteJelly bellyTango RTK activity assayWing hearts

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