Receptor-mediated endocytosis of the low-density-lipoprotein receptor (LDLR) mediates the internalisation of LDL-cholesterol into cells. On page 3961, Vilja Pietiäinen, Elina Ikonen and colleagues describe a role for N-myc downstream regulated gene 1 (NDRG1) in cellular lipid homeostasis and endocytic trafficking of the LDLR. Mutations in NDRG1 are known to cause the demyelinating neuropathy Charcot–Marie–Tooth disease type 4D, but the little is known about the cellular function of NDRG1. Using small interfering RNAs to silence NDRG1 in A431 cells, the authors report reduced uptake of LDL-cholesterol owing to decreased levels of LDLR at the plasma membrane and diminished LDLR degradation. Moreover, LDLR accumulated in modified early endosomes and multivesicular bodies (MVBs), which had increased numbers of ceramide-enriched intraluminal vesicles. Depletion of NDRG1 also resulted in increased amounts of ubiquitylated LDLR, despite reduced levels of endosomal sorting complex required for transport (ESCRT) proteins. The authors next silenced the E3 ubiquitin ligase IDOL to prevent LDLR ubiquitylation in the NDRG1-depleted cells, and found that the LDLR seemed to be recycled to the plasma membrane, rescuing plasma membrane LDLR levels and LDL uptake. Finally, the authors studied the effects of silencing Ndrg1 in mouse oligodendrocytes, finding that there was reduced uptake of LDL and downregulation of OLIG2, the oligodendrocyte differentiation factor – these effects were rescued by co-depletion of Idol. NDRG1 has therefore been identified as a novel regulator of MVB integrity and LDLR endosomal recycling.
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IN THIS ISSUE| 01 September 2013
NDRG1 in LDLR trafficking
Online Issn: 1477-9137
Print Issn: 0021-9533
© 2013. Published by The Company of Biologists Ltd
J Cell Sci (2013) 126 (17): e1705.
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NDRG1 in LDLR trafficking. J Cell Sci 1 September 2013; 126 (17): e1705. doi:
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