A genetic screen to identify novel interactions of the phosphatidylinositol phosphate signaling pathway in Drosophila spermatogenesis
- 1The Hospital for Sick Children
Abstract
Phosphatidylinositol (PI) phosphates (PIPs) are membrane lipids with crucial roles in intracellular signaling, membrane trafficking and cytoskeletal organization. To perturb PIP function in Drosophila melanogaster sperm development, we previously expressed the Salmonella PIP phosphatase SigD (also known as SopB) under control of a spermatocyte- specific promoter. SigD expression results in reduced levels of plasma membrane PI 4,5-bisphosphate [PI(4,5)P2; henceforth PIP2] and male sterility. Transgenic lines expressing high levels of SigD (SigD-high) exhibit defects in spermatocyte cytokinesis, ciliary transition zone maturation and spermatid elongation, whereas lines expressing low levels of SigD (SigD-low) have defects in nuclear shaping and spermatid cell polarization. To further investigate the role of PIPs during Drosophila sperm development, we conducted a sensitized genetic screen to identify suppressors and enhancers of SigD-low phenotypes. From a screen of 760 chromosomal deficiencies spanning 83.6% of chromosomes 2 and 3, we identified 80 interacting regions that were further narrowed down to 40 individual suppressors. Among the strongest interactors were genes involved in microtubule dynamics, nucleocytoplasmic transport and membrane trafficking. The novel genetic interactions identified by our screen pave the way for further investigation into molecular mechanisms underlying the affected aspects of sperm development.
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BibTeX
@misc{rossini2026genetic,
title = {{A genetic screen to identify novel interactions of the phosphatidylinositol phosphate signaling pathway in Drosophila spermatogenesis}},
author = {S. Rossini and N. Nasirzadeh and M. S. Icmat and F. H.-K. Chu and M. Rana and K. Micovic and K. Singh and J. Zhuo and L. Shao and A. Ohri and K. Huang and M. Lightwala and M. S. Nagree and T. Jiwani and K. Bellamkonda and P. Prasad and L. Antonyan and H. Lands and G. Sesso and L. Liu and N. F. Liu and A. Philson and D. Sheykhkarimli and P. Krithivasan and A. Papadopoli and L. Fabian and J. A. Brill},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754494},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754494v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A genetic screen to identify novel interactions of the phosphatidylinositol phosphate signaling pathway in Drosophila spermatogenesis
AU - S. Rossini
AU - N. Nasirzadeh
AU - M. S. Icmat
AU - F. H.-K. Chu
AU - M. Rana
AU - K. Micovic
AU - K. Singh
AU - J. Zhuo
AU - L. Shao
AU - A. Ohri
AU - K. Huang
AU - M. Lightwala
AU - M. S. Nagree
AU - T. Jiwani
AU - K. Bellamkonda
AU - P. Prasad
AU - L. Antonyan
AU - H. Lands
AU - G. Sesso
AU - L. Liu
AU - N. F. Liu
AU - A. Philson
AU - D. Sheykhkarimli
AU - P. Krithivasan
AU - A. Papadopoli
AU - L. Fabian
AU - J. A. Brill
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754494
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754494v1
AB - Phosphatidylinositol (PI) phosphates (PIPs) are membrane lipids with crucial roles in intracellular signaling, membrane trafficking and cytoskeletal organization. To perturb PIP function in Drosophila melanogaster sperm development, we previously expressed the Salmonella PIP phosphatase SigD (also known as SopB) under control of a spermatocyte- specific promoter. SigD expression results in reduced levels of plasma membrane PI 4,5-bisphosphate [PI(4,5)P2; henceforth PIP2] and male sterility. Transgenic lines expressing high levels of SigD (SigD-high) exhibit defects in spermatocyte cytokinesis, ciliary transition zone maturation and spermatid elongation, whereas lines expressing low levels of SigD (SigD-low) have defects in nuclear shaping and spermatid cell polarization. To further investigate the role of PIPs during Drosophila sperm development, we conducted a sensitized genetic screen to identify suppressors and enhancers of SigD-low phenotypes. From a screen of 760 chromosomal deficiencies spanning 83.6% of chromosomes 2 and 3, we identified 80 interacting regions that were further narrowed down to 40 individual suppressors. Among the strongest interactors were genes involved in microtubule dynamics, nucleocytoplasmic transport and membrane trafficking. The novel genetic interactions identified by our screen pave the way for further investigation into molecular mechanisms underlying the affected aspects of sperm development.
ER -