Investigation of three centrosome/ciliary proteins roles in ciliary function maintenance in Drosophila

Abstract

The study of ciliary maintenance is critical for understanding age-related functional decline, as defects in these organelles contribute to widespread neurodegenerative and sensory disorders. This research investigated the functional role of four conserved ciliopathy-related genes—ALMS-1, CFAP410, GUCY2D,—in age-associated motor and longevity phenotypes in Drosophila melanogaster. Comprehensive Negative Geotaxis and Longevity Assays were conducted on various mutant lines. The results demonstrated a clear correlation between ciliary gene dysfunction and accelerated aging phenotypes. All mutant lines exhibited an accelerated decline in locomotor performance and reduced lifespan when compared to the control. Findings were gene- and isoform-specific: the ALMS-1a mutant displayed severe, early-onset functional collapse and the shortest lifespan, while the ALMS-1b mutant maintained performance for a longer duration. The CFAP410 mutant lines exhibited a pronounced age-dependent loss of locomotor performance, with the single-isoform CFAP410a displaying extreme functional deficits early in life. Crucially, the Olfaction Assay highlighted differential mechanisms of sensory failure: the progressive deficit in GUCY2D mutants is due to a failure in active signal termination (sustained attraction at middle age), supporting the theory that DmGucy2d is disrupted as an Intraflagellar Transport (IFT) cargo. Conversely, the CFAP410 mutants showed a rapid and total loss of function in late adulthood, consistent with the catastrophic collapse resulting from a structural protein defect. These findings establish that specific defects in ciliary regulatory genes drive accelerated behavioral decline that strongly phenocopies symptoms of human neurodegenerative disorders and ciliopathies.