Biology subjects

Kang, P. J.

Publications and source records attributed to Kang, P. J..

4 recordsLinked to original sources

bioRxiv2025

Reconstructing the Ischemic Cerebrum by Transplanted Human Neurons

Neural transplantation holds the potential to repair damaged neural circuits in neurological diseases. However, it remains unknown how the grafted neurons project axons to and make functional connections with the appropriate targets to repair the damaged circuit at the adult stage. Here we report that human cortical progenitors, transplanted into the ischemic mouse motor cortex, matured and integrated into cortical and subcortical neural circuits including the corticospinal tract. Neuronal tracing combined with single-nuclei RNA sequencing revealed the close relationship between the transcription profiles of a cortical neuronal subtype, especially those of axon guidance and synapse assembly, with the specific target projection and synapse organization. Machine learning-based regression further identified the transcriptional codes for the targeted projection and circuit integration to reconstruct the damaged circuits. Our finding opens a promising strategy for treating neurological diseases through promoting regeneration and neural transplantation. HighlightsHuman ESC-derived cortical neurons reconstitute the ischemic motor cortex Functionally repaired corticospinal tract restores animal behaviors Transplanted cortical neurons exhibit subtype-specific projection and integration Unique transcriptional coding for axonal navigation in the mature CNS

neuroscience↗

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↗