Figure 2.

Working model of endosomal trafficking of LDLR. Following endocytosis, LDLR is transported to endosomes, where the receptor is directed to the late endosomes and lysosomes for PCSK9- or IDOL-mediated degradation or is retrieved from this pathway and recycled back to the plasma membrane. The CCC complex is known to facilitate recycling of LDLR by a direct interaction between CCC subunit COMMD1 with LDLR, whereas WASH drives formation of actin patches on endosomal sorting domains to regulate LDLR recycling. Although the function of retromer and retriever in LDLR recycling has not been fully elucidated, retromer might facilitate LDLR recycling by recruiting CCC and WASH complexes to the endosomal membrane, and retriever might regulate LDLR retrieval and recycling by coupling to SNX17, an adaptor protein binding to the NPxY-motif in the cytosolic tail of LDLR. ESCRT = endosomal sorting complex required for transport; Ub = ubiquitin.