Constitutive Internalization of the Leucine-Rich G Protein-Coupled Receptor-5 (LGR5) to the Trans-Golgi Network

The study investigated the intracellular trafficking of the leucine-rich G protein-coupled receptor-5 (LGR5), a key marker in stem cells across various tissues, including hair follicles. Researchers found that LGR5 predominantly resides intracellularly, undergoing constitutive internalization to the trans-Golgi network (TGN) via a specific motif at its C terminus. This process was shown to depend on dynamin GTPase activity, with LGR5 internalizing into EEA1- and Rab5-positive endosomes but not recycling rapidly to the plasma membrane. Instead, LGR5 transits through Rab7- and Rab9-positive vesicles and co-localizes with the retromer complex component Vps26, reaching a steady-state in the TGN within 2 hours. Mutagenesis revealed that serine 861 and 864 are crucial for this internalization. The findings suggested potential novel biochemical roles for LGR5 in the Wnt signaling pathway.