Emergence of Dip2-mediated Specific DAG-based PKC Signalling Axis in Eukaryotes

Shambhavi, S.; Mondal, S.; Chakraborty, A.; Shukla, N.; Panda, B. K.; Kumar, S.; Kinatukara, P.; Pal, B.; Kamat, S. S.; Sankaranarayanan, R.

doi:10.1101/2024.10.15.618531

bioRxiv · 10.1101/2024.10.15.618531

Emergence of Dip2-mediated Specific DAG-based PKC Signalling Axis in Eukaryotes

Shambhavi, S.·Mondal, S.·Chakraborty, A.·Shukla, N.·Panda, B. K.·Kumar, S.·Kinatukara, P.·Pal, B.·Kamat, S. S.·Sankaranarayanan, R.

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Abstract

Diacylglycerols (DAGs) are used for metabolic purposes and are tightly regulated secondary lipid messengers in eukaryotes. DAG subspecies with different fatty-acyl chains are proposed to be involved in the activation of distinct PKC isoforms, resulting in diverse physiological outcomes. However, the molecular players and the regulatory origin for fine-tuning the PKC pathway are unknown. Here, we show that Dip2, a conserved DAG regulator across Fungi and Animalia, has emerged as a modulator of PKC signalling in yeast. Dip2 maintains the level of a specific DAG subpopulation, required for the activation of PKC-mediated cell wall integrity pathway. Interestingly, the canonical DAG-metabolism pathways, being promiscuous, are decoupled from PKC signalling. We demonstrate that these DAG subspecies are sourced from a phosphatidylinositol pool generated by the acyl-chain remodelling pathway. Furthermore, we provide insights into the intimate coevolutionary relationship between the regulator (Dip2) and the effector (PKC) of DAG-based signalling. Hence, our study underscores the establishment of Dip2-PKC axis about 1.2 billion years ago in Opisthokonta, which marks the rooting of the first specific DAG-based signalling module of eukaryotes.

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Shambhavi, S., Mondal, S., Chakraborty, A., Shukla, N., Panda, B. K., Kumar, S., Kinatukara, P., Pal, B., Kamat, S. S., Sankaranarayanan, R.. 2024-10-16. Emergence of Dip2-mediated Specific DAG-based PKC Signalling Axis in Eukaryotes. https://doi.org/10.1101/2024.10.15.618531

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