eLIFE
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.
| 论文编号: | DOI:10.7554/eLife.58069 |
| 论文题目: | BLOS1 Mediates Kinesin Switch during Endosomal Recycling of LDL Receptor |
| 英文论文题目: | BLOS1 Mediates Kinesin Switch during Endosomal Recycling of LDL Receptor |
| 第一作者: | Chang Zhang, Chanjuan Hao, Guanghou Shui, Wei Li |
| 英文第一作者: | Chang Zhang, Chanjuan Hao, Guanghou Shui, Wei Li |
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| 发表年度: | 2020-11-16 |
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| 摘要: | 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. |
| 英文摘要: | 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. |
| 刊物名称: | eLIFE |
| 英文刊物名称: | eLIFE |
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| 其它备注: | Chang Zhang, Chanjuan Hao, Guanghou Shui, Wei Li. BLOS1 Mediates Kinesin Switch during Endosomal Recycling of LDL Receptor. eLIFE. DOI:10.7554/eLife.58069 |
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