Emergence of Dip2-mediated specific DAG-based PKC signalling axis in eukaryotes.

Area of Science:

• Lipid signaling
• Molecular biology
• Evolutionary biology

Background:

• Diacylglycerols (DAGs) are crucial lipid messengers regulating diverse cellular processes.
• Specific DAG subspecies are implicated in activating distinct protein kinase C (PKC) isoforms, but the underlying regulatory mechanisms remain unclear.

Purpose of the Study:

• To identify molecular players and regulatory origins for fine-tuning PKC signaling.
• To investigate the role of Dip2 in DAG metabolism and PKC pathway modulation in yeast.

Main Methods:

• Investigated the function of Dip2 in yeast.
• Analyzed DAG subspecies levels and their relationship with PKC signaling.
• Traced the origin of specific DAG subspecies.

Main Results:

• Dip2 was identified as a conserved DAG regulator that modulates PKC signaling in yeast.
• Dip2 maintains specific DAG levels essential for PKC-mediated cell wall integrity.
• Canonical DAG metabolism pathways are decoupled from PKC signaling, with DAG subspecies originating from phosphatidylinositol remodeling.

Conclusions:

• The Dip2-PKC axis represents the first specific DAG-based signaling module in eukaryotes, established approximately 1.2 billion years ago.
• This study elucidates a novel regulatory mechanism for DAG-based signaling and its evolutionary significance.