The conserved alternative splicing factor caper regulates neuromuscular phenotypes during development and aging.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• RNA-binding proteins regulate gene expression post-transcriptionally, vital for nervous system function.
• Mutations in RNA splicing factors are linked to neurodegenerative and neurodevelopmental disorders.
• The conserved alternative splicing factor Caper is essential for sensory neural subtype development in Drosophila.

Purpose of the Study:

• To investigate the role of Caper in neuromuscular junction (NMJ) development and locomotor behavior.
• To determine the tissue-specific requirement of Caper in the nervous system versus muscle.
• To explore Caper's interaction with other RNA-binding proteins and its relevance to neurodegenerative disease phenotypes.

Main Methods:

• Utilized Drosophila melanogaster as a model organism.
• Assessed NMJ morphogenesis through genetic manipulation of Caper.
• Evaluated larval and adult locomotor behavior.
• Investigated Caper's interaction with the RNA-binding protein Fmrp.
• Analyzed sex and age-biased phenotypes.

Main Results:

• Caper dysfunction results in aberrant NMJ morphogenesis and abnormal larval/adult locomotor behavior.
• Caper's function is more critical in the nervous system than in muscle for NMJ development and locomotor regulation.
• Caper interacts with Fmrp to regulate adult locomotor behavior.
• Caper dysfunction phenotypes exhibit sex and age biases, mirroring human neurodegenerative disorders.

Conclusions:

• Caper is essential for proper nervous system development, NMJ formation, and motor control.
• The nervous system-specific role of Caper highlights its importance in neuronal function.
• Caper's interaction with Fmrp and its age/sex-biased phenotypes provide insights into the molecular basis of neurodegenerative diseases.