Biology subjects

Widuch, M. J.

Publications and source records attributed to Widuch, M. J..

2 recordsLinked to original sources

bioRxiv2026

The microprotein Dafcin resembles influenza HA fusion peptide and regulates the size of storage lysosomes in the germline

Microproteins translated from short open reading frames are increasingly understood to play important roles in cell biology and development. Here, we describe a microprotein in Drosophila that is expressed in ovarian follicle cells which surround the developing oocyte. The Dafcin microprotein is predicted to form an amphipathic alpha-helix, a structure known to interact with lipid bilayers. Dafcins structure most resembles the influenza HA fusion peptide, which induces negative curvature of endosomal membranes. Dafcin tagged with GFP localizes to the Golgi and is ultimately secreted from the follicle cells. Remarkably, this occurs without the microprotein having a secretory signal sequence. The protein is taken up into the oocyte by endocytosis, localizing to the inner face of storage lysosomes called yolk granules. Mutant analysis shows that Dafcin is required to limit the size of yolk granules. This may occur by inducing negative membrane curvature like HA peptide. In support, liposomes formed in vitro with both Dafcin and HA peptides are smaller in size.

cell biology↗

bioRxiv2026

Insulin Signaling Functions as a Topological Switch That Couples Aging and Heat Stress Responsiveness

While aging and thermal stress are phenotypically intertwined, their transcriptomic signatures remain paradoxically distinct in Drosophila. Here, we demonstrate that this parallel modularity is not an inherent genomic constraint but is actively maintained by Insulin/IGF-1 signaling (IIS). Using transcriptomic analysis, we show that high IIS activity partitions the genome into orthogonal regulatory layers where aging and heat stress function as independent additive inputs. Systemic attenuation of IIS triggers a transition to an integrated architecture. In this state, the genomes perception of heat stress becomes age-dependent, enabling a hyper-adaptive induction of heat shock proteins in old adults--effectively reversing the typical age-related decline in proteostasis. We propose that the IIS pathway functions as a topological switch, shifting the genome from a modular growth-mode to an integrated maintenance-mode. Thus, dampening the response to heat stress with age is an adaptable regulatory state rather than an inevitable consequence of cellular senescence.

systems biology↗