Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of endocytosis.
Early endosomes have a membrane enriched in phosphatidylinositol 3-phosphate, also known as PtdIns(3)P, which regulates almost all sorting events in the early endosome along with two Ras-associated binding proteins or Rab proteins. Rabs localized in the early endosome, namely Rab4 and Rab5, are GTP-binding proteins that are active when bound to GTP and inactive when bound to GDP. Rab5 is extensively studied for several functions that it regulates, such as entry of endocytosed material into early endosomes, generation of phosphatidylinositol 3-phosphate, and movement of early endosomes along the microtubules. Rab4 regulates the recycling of receptors from the early endosome to the plasma membrane.
Improper protein sorting in the early endosome or loss of regulatory control in the sorting process can cause aberrant endosomal functions, leading to various neurological conditions such as Alzheimer’s disease, Huntington’s disease, or Down’s syndrome.
Despite the several important roles early endosomes play, their fundamental characteristics are not yet fully understood. For example, the mechanisms underlying the selection of specific Rab proteins for localization into the early endosomes are still unknown. It is also unclear if different early endosomes are involved in the sorting of different types of receptors. Additionally, early endosomes do not have distinct membrane markers that can be easily identified through light microscopy, making it difficult to distinguish them from other types of endosomes. Therefore, early endosomes are a yet-evolving topic of investigation.
