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

Summary

Researchers developed a new method to track when and where a specific signaling protein called Alk is active in fruit fly hearts. They discovered that Alk is switched on in heart muscle cells of developing and adult flies, with a nearby protein called Jeb acting as the activating signal. When they increased Alk signaling artificially, flies developed irregular heartbeats and had shorter lifespans, especially under heat stress, revealing an important role for this protein in maintaining healthy heart function.

Background

Anaplastic lymphoma kinase (Alk) signaling is a receptor tyrosine kinase important in cell specification, metabolic regulation, and cancer. While Alk expression has been documented in nervous system tissues, its role in cardiac tissues has not been previously investigated in Drosophila or thoroughly characterized in vertebrate systems.

Objective

To develop an Alk activity reporter system to map endogenous Alk signaling during Drosophila development and investigate previously unknown roles for Alk signaling in cardiac tissues.

Results

Alk Tango revealed active Alk signaling in larval and adult cardiomyocytes with Jeb ligand expression in adjacent pericardial cells. Cardiac Alk overexpression induced cardiac arrhythmia, irregular muscle contraction, and wing heart hyperplasia, while decreasing adult survival and fitness under heat stress. Alk was not required for embryonic heart development but affected later cardiac function.

Conclusion

This study identifies a novel role for Jeb/Alk signaling in Drosophila cardiac function distinct from its embryonic developmental role. The findings suggest potential evolutionary conservation of ALK signaling in vertebrate hearts and may have implications for understanding ALK-related cardiac complications in human patients.
  • Published in:Cell Communication and Signaling,
  • Study Type:Experimental Research Study,
  • Source: PMID: 40382638, DOI: 10.1186/s12964-025-02150-x
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