Related Experiment Video
Updated: May 27, 2025

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
Context-specific interaction of the lipid regulator DIP-2 with phospholipid synthesis in axon regeneration and
Abstract:
Neurons maintain their morphology over prolonged periods of adult life with limited regeneration after injury. C. elegans DIP-2 is a conserved regulator of lipid metabolism that affects axon maintenance and regeneration after injury. Here, we investigated genetic interactions of dip-2 with mutants in genes involved in lipid biosynthesis and identified roles of phospholipids in axon regrowth and maintenance. CEPT-2 and EPT-1 are enzymes catalyzing the final steps in the de novo phospholipid synthesis (Kennedy) pathway. Loss of function mutants of cept-2 or ept-1 show reduced axon regrowth and failure to maintain axon morphology. We demonstrate that CEPT-2 is cell-autonomously required to prevent age-related axonal defects. Interestingly, loss of function in dip-2 led to suppression of the axon regrowth phenotype observed in either cept-2 or ept-2 mutants, suggesting that DIP-2 acts to counterbalance phospholipid synthesis. Our findings reveal the genetic regulation of lipid metabolism to be critical for axon maintenance under injury and during aging.
Article Summary:
Little is known about how adult neurons live long with limited regenerative capacity. This study investigates the role of lipid metabolism in sustaining neuronal health in C. elegans. Mutating phospholipid synthetic genes impairs axon regrowth after injury. Lack of DIP-2, a lipid regulator, restores regrowth, suggesting DIP-2 counterbalances phospholipid synthesis. Moreover, neuronal phospholipid synthesis is essential for preventing age-dependent axonal defects. These findings reveal phospholipid biosynthesis is key to axon integrity during aging and injury. As lipid metabolism is implicated in neurological disorders, this study serves as an entry point into investigating neuronal lipid biology under various conditions.
Related Concept Videos
Neurogenesis and Regeneration of Nervous Tissue
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
IP3/DAG Signaling Pathway
Synthesis of Phosphatidylcholine in the ER Membrane
The major components of all eukaryotic cell...
Asymmetric Lipid Bilayer
Assembly of the Lipid Bilayer in the ER
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...

