Biology subjects

Park, H.-O.

Publications and source records attributed to Park, H.-O..

4 recordsLinked to original sources

bioRxiv2025

Cdc42 Partitioning by Chaperone Ydj1 During Asymmetric Division and Aging in Yeast

Cdc42, a small GTPase crucial for cell polarity, often becomes hyperactive with age and contributes to senescence and aging in yeast and animal cells. However, the mechanisms underlying its age-related upregulation are not well understood. Here, we report that in budding yeast, Cdc42 accumulates over successive divisions and that lowering its levels can extend lifespan. Using microfluidics-assisted live-cell imaging and genetic analysis, we found that Cdc42 is distributed unevenly between mother and daughter cells during division. Daughter cells inherit lower levels of Cdc42, which likely helps them remain young. This asymmetric distribution depends on Cdc42s localization to endomembranes and involves Ydj1, a farnesylated Hsp40/DnaJ chaperone anchored to the endoplasmic reticulum (ER). Ydj1 interacts with Cdc42, enhancing its stability and proper partitioning during cell division. We thus propose that ER-bound Ydj1 facilitates the asymmetric distribution of Cdc42, limiting aging to mother cells. We thus propose that ER-bound Ydj1 facilitates the asymmetric distribution of Cdc42, limiting aging to mother cells.

cell biology↗

bioRxiv2023

Cdc42 couples septin recruitment to the axial landmark assembly via Axl2 in budding yeast

Cell polarization generally occurs along a single axis that is directed by a spatial cue. Cells of the budding yeast Saccharomyces cerevisiae undergo polarized growth and oriented cell division in a spatial pattern by selecting a specific bud site. Haploid a or cells bud in the axial pattern in response to a transient landmark that includes Bud3, Bud4, Axl1, and Axl2. Septins, a family of filament-forming GTP-binding proteins, are also involved in axial budding and recruited to an incipient bud site, but the mechanism of recruitment remains unclear. Here, we show that Axl2 interacts with Bud3 and the Cdc42 GTPase in its GTP-bound state. Axl2 also interacts with Cdc10, a septin subunit, promoting efficient recruitment of septins near the cell division site. Furthermore, a cdc42 mutant defective in the axial budding pattern at a semi-permissive temperature had a reduced interaction with Axl2 and compromised septin recruitment in the G1 phase. We thus propose that active Cdc42 brings Axl2 to the Bud3-Bud4 complex and that Axl2 then interacts with Cdc10, linking septin recruitment to the axial landmark.

cell biology↗

bioRxiv2021

Upregulation of the Cdc42 GTPase limits replicative lifespan in budding yeast

Cdc42, a conserved Rho GTPase, plays a central role in polarity establishment in yeast and animals. Cell polarity is critical for asymmetric cell division, and asymmetric cell division underlies replicative aging of budding yeast. Yet how Cdc42 and other polarity factors impact lifespan is largely unknown. Here, we show by live-cell imaging that the active Cdc42 level is sporadically elevated in wild type during repeated cell divisions but rarely in the long-lived bud8 deletion cells. We find a novel Bud8 localization with cytokinesis remnants, which also recruit Rga1, a Cdc42 GTPase activating protein. Genetic analyses and live-cell imaging suggest that Rga1 and Bud8 oppositely impact lifespan likely by modulating active Cdc42 levels. An rga1 mutant, which has a shorter lifespan, dies at the unbudded state with a defect in polarity establishment. Remarkably, Cdc42 accumulates in old cells, and its mild overexpression accelerates aging with frequent symmetric cell divisions, despite no harmful effects on young cells. Our findings implicate that the interplay among these positive and negative polarity factors limits the lifespan of budding yeast.

cell biology↗

bioRxiv2019

Temporal regulation of cell polarity via the interaction of the Ras GTPase Rsr1 and the scaffold protein Bem1

Establishing cell polarity is critical for growth and development of most organisms. The Cdc42 GTPase plays a central role in polarity development in species ranging from yeast to humans. In budding yeast, a specific growth site (i.e. bud site) is selected in the G1 phase, which determines the axis of cell polarization. Rsr1, a Ras GTPase, interacts with Cdc42 and its associated proteins to promote polarized growth at the proper bud site. Yet the mechanism underlying spatial cue-directed cell polarization is not fully understood. Here, we show that Rsr1 associates with Bem1, a scaffold protein, preferentially in its GDP-bound state in early G1. This interaction involves a part of the Bem1 Phox homology (PX) domain, which overlaps with a region previously shown to interact with Exo70, an exocyst component. Furthermore, overexpression of the constitutively GDP-bound Rsr1 interferes with Bem1s association with Exo70 and inhibits Bem1-dependent Exo70 polarization. We propose that Rsr1 plays a delicate role in coordination of spatial and temporal regulation of polarity establishment via its GTP- and GDP-bound states.

cell biology↗