Yolk proteins (vitellogenins, VITs) are crucial lipid-carrying molecules that supply nutrients from the mother to embryos in oviparous animals. In humans, their functional analog apolipoprotein B-100 (apoB-100) is a core component of low-density and very low-density lipoproteins (LDL and VLDL, respectively), playing a pivotal role in systemic lipid transport. Understanding how these lipoproteins are secreted may help unravel the mechanisms underlying conditions like atherosclerosis and fatty liver disease.
In a recent article published in Life Metabolism, researchers report that VIT secretion in Caenorhabditis elegans is mediated by both the classical secretory pathway and the recycling endosome (RE) system.
The team used genetic screens, imaging, and electron microscopy to show that after being synthesized in the rough endoplasmic reticulum (ER), VIT is trafficked via the Golgi apparatus and then follows two distinct routes: direct secretion at the basolateral membrane, and an alternative pathway involving REs marked by the protein RME-1. Both newly synthesized and endocytosed VIT were found to be rerouted through REs before entering the body cavity for embryo uptake.
Furthermore, they discovered that the GTPase RAB-10 is essential for transporting VIT-containing vesicles (VVs) from the apical to the basolateral side of the intestinal cells, facilitating proper VIT secretion. Loss of RAB-10 disrupted the localization of RME-1 and led to VIT accumulation in the intestine, confirming its role in regulating RE function.
Importantly, these findings demonstrate that REs not only support the re-secretion of recycled VIT but also participate directly in the trafficking of newly synthesized VIT (Figure 1), a mechanism not previously reported in the context of mammalian apoB-100.
This study presents a comprehensive model of yolk protein secretion in C. elegans, integrating classical secretion with membrane recycling pathways. It provides new insights into how apolipoproteins like apoB-100 are secreted in mammals, with potential implications for lipid metabolism and related diseases.
DOI：https://doi.org/10.1093/lifemeta/loaf026