What question did this study set out to answer?

Investigate the molecular mechanisms and functional consequences of 19 nonsynonymous NPC1L1 variants identified in individuals with low cholesterol absorption.

December 29, 2010Journal of Biological ChemistryOpen Access

Molecular Characterization of the NPC1L1 Variants Identified from Cholesterol Low Absorbers

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Authors

LWLijuan WangGanzhou People's Hospital JWJing WangChinese Academy of Sciences NLNa LiLanzhou University

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Implication

Experimental study uncovers distinct trafficking and degradation defects across 19 NPC1L1 variants, indicating how specific mutations impair human cholesterol absorption.

Key Points

Investigate the molecular mechanisms and functional consequences of 19 nonsynonymous NPC1L1 variants identified in individuals with low cholesterol absorption.
Measured cellular cholesterol uptake across 19 human nonsynonymous NPC1L1 variants in vitro.
Assessed protein stability, recycling, subcellular localization, glycosylation, and involvement of the ER-associated degradation (ERAD) pathway.
Evaluated hepatic localization and biliary cholesterol re-absorption in vivo using adenovirus-mediated gene transfer in mice for selected variants.
Eight variants partially retained cholesterol uptake while exhibiting mild defects in recycling, localization, glycosylation, or stability.
Eleven variants were severely dysfunctional, failed to mediate cholesterol uptake, and were rapidly eliminated via ER-associated degradation.
Adenoviral delivery in mice demonstrated that S881L failed to target the liver canalicular membrane and impaired biliary cholesterol re-absorption, whereas G402S mirrored wild-type protein function.

Cite This Study

Wang et al. (2010) studied this question.

synapsesocial.com/papers/6a9130d9dc264a2e5a11f910 https://doi.org/10.1074/jbc.m110.178368

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Implication

Experimental study uncovers distinct trafficking and degradation defects across 19 NPC1L1 variants, indicating how specific mutations impair human cholesterol absorption.

Molecular Characterization of the NPC1L1 Variants Identified from Cholesterol Low Absorbers

Discussion

Member takes

Implication

Key Points

Cite This Study

Molecular Characterization of the NPC1L1 Variants Identified from Cholesterol Low Absorbers

Discussion

Member takes

Implication

Key Points

Cite This Study

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