BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor
- Capital Medical Universtiy, China
- Chinese Academy of Sciences, China
Abstract
Low-density lipoprotein receptor (LDLR) in hepatocytes plays a key role in normal clearance of circulating LDL and in whole body cholesterol homeostasis. The trafficking of LDLR is highly regulated in clathrin-dependent endocytosis, endosomal recycling and lysosomal degradation. Current studies focus on its endocytosis and degradation. However, the detailed molecular and cellular mechanisms underlying its endosomal recycling are largely unknown. We found that BLOS1, a shared subunit of BLOC-1 and BORC, is involved in LDLR endosomal recycling. Loss of BLOS1 leads to less membrane LDLR and impairs LDL clearance from plasma in hepatocyte-specific BLOS1 knockout mice. BLOS1 interacts with kinesin-3 motor KIF13A, and BLOS1 acts as a new adaptor for kinesin-2 motor KIF3 to coordinate kinesin-3 and kinesin-2 during the long-range transport of recycling endosomes (REs) to plasma membrane along microtubule tracks to overcome hurdles at microtubule intersections. This provides new insights into RE's anterograde transport and the pathogenesis of dyslipidemia.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Ministry of Science and Technology of the People's Republic of China (2019YFA0802104)
- Wei Li
National Natural Science Foundation of China (31830054; 91539204)
- Wei Li
National Natural Science Foundation of China (91954104; 81670789)
- Chanjuan Hao
Chinese Academy of Sciences (XDA12030211)
- Guanghou Shui
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work was approved by the Institutional Animal Care and Use Committee of the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (mouse protocol KYD2005-006).
Copyright
© 2020, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor
eLife 9:e58069.
https://doi.org/10.7554/eLife.58069
