Biology subjects

Jacobs, K. C.

Publications and source records attributed to Jacobs, K. C..

4 recordsLinked to original sources

bioRxiv2026

The extracellular matrix gene mec-9 regulates C. elegans sensory cilia

Cilia are critical sensory organelles that project from the cell surface into the tissue environment, where they are surrounded by extracellular matrix (ECM). Abnormal ECM and fibrosis are two hallmarks of ciliopathies, yet the relationship between cilia and ECM is not well understood. Using the sense organs of C. elegans as a model, we found that a neomorphic mutation in the ECM gene mec-9 impacts sensory cilia function, ciliary protein localization, microtubule ultrastructure, and shedding of ciliary extracellular vesicles (EVs). We show that mec-9 is not expressed in EV releasing neurons, but rather by companion neurons in the sense organs, and may act cell non-autonomously. Our studies reveal pleiotropic roles for mec-9 in the C. elegans ciliated nervous system and provide an in vivo model to study the relationship between cilia and ECM.

cell biology↗

bioRxiv2024

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

Therapeutic use of tiny extracellular vesicles (EVs) requires understanding cargo loading mechanisms. Here, we used a modular proximity label approach to identify EV cargo associated with the transient potential channel (TRP) polycystin PKD-2 of C. elegans. Polycystins are conserved receptor-TRP channel proteins affecting cilium function; dysfunction causes polycystic kidney disease in humans and mating deficits in C. elegans. Polycystin-2 EV localization is conserved from algae to humans, hinting at an ancient and unknown function. We discovered that polycystins associate with and direct specific cargo to EVs: channel-like PACL-1, dorsal and ventral membrane C-type lectins PAMLs, and conserved tumor necrosis-associated factor (TRAF) signaling adaptors TRF-1 and TRF-2. Loading of these components relied on polycystin-1 LOV-1. Our modular EV-TurboID approach can be applied in both cell- and tissue-specific manners to define the composition of distinct EV subtypes, addressing a major challenge of the EV field.

cell biology↗

bioRxiv2022

Mechanism of commitment to a mating partner in Saccharomyces cerevisiae

Many cells detect and follow gradients of chemical signals to perform their functions. Yeast cells use gradients of extracellular pheromones to locate mating partners, providing a tractable model to understand how cells decode the spatial information in gradients. To mate, yeast cells must orient polarity toward the mating partner. Polarity sites are mobile, exploring the cell cortex until they reach the proper position, where they stop moving and "commit" to the partner. A simple model to explain commitment posits that a high concentration of pheromone is only detected upon alignment of partner cells polarity sites, and causes polarity site movement to stop. Here we explore how yeast cells respond to partners that make different amounts of pheromone. Commitment was surprisingly robust to varying pheromone levels, ruling out the simple model. We also tested whether adaptive pathways were responsible for the robustness of commitment, but our results show that cells lacking those pathways were still able to accommodate changes in pheromone. To explain this robustness, we suggest that the steep pheromone gradients near each mating partners polarity site trap the polarity site in place. This mechanism has evolutionary implications because it enables sexual selection for cells making more pheromone.

cell biology↗

bioRxiv2018

Mating in wild yeast: variable interest in sex after spore germination

Studies of lab strains of Saccharomyces cerevisiae have uncovered signaling pathways involved in mating, including information processing strategies to optimize decisions to mate or to bud. However, lab strains are heterothallic (unable to self-mate) while wild yeast are homothallic. And while mating of lab strains is studied using cycling haploid cells, mating of wild yeast is thought to involve germinating spores. Thus, it was unclear whether lab strategies would be appropriate in the wild. Here, we have investigated the behaviors of several yeast strains derived from wild isolates. Following germination, these strains displayed large differences in their propensity to mate or to enter the cell cycle. The variable interest in sex following germination was correlated with differences in pheromone production, which were due to both cis- and trans-acting factors. Our findings suggest that yeast spores germinating in the wild may often enter the cell cycle and form microcolonies prior to engaging in mating.

cell biology↗