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Updated: Sep 9, 2025
11:05
Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
Published on: February 21, 2019
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LDL transcytosis passes through the trans-Golgi network and requires Rab10
Tse Wing Winnie Ho1, Changsen Wang2, Warren L Lee3
1Keenan Centre for Biomedical Research, St. Michael's Hospital, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Journal of Lipid Research
|September 3, 2025
Summary
Low-density lipoprotein (LDL) transcytosis involves the Golgi apparatus, with Rab proteins regulating this process. Specific Rab proteins, Rab6a and Rab10, are crucial for LDL transport across endothelial cells.
Area of Science:
- Endothelial cell biology
- Lipid metabolism
- Molecular cell biology
Background:
- Atherosclerosis pathogenesis involves subendothelial retention of low-density lipoproteins (LDL).
- Endothelial LDL transcytosis, mediated by SR-BI and ALK1, is crucial but its intracellular mechanisms are unclear.
- Low-density lipoprotein receptor (LDLR) is typically not involved in this process.
Purpose of the Study:
- To elucidate the intracellular mechanisms and route of LDL transcytosis across endothelial cells.
- To identify key intracellular proteins regulating LDL transcytosis.
- To investigate the role of Rab proteins in LDL transport.
Main Methods:
- Total internal reflection fluorescence microscopy in LDLR-depleted human coronary artery endothelial cells (HCAECs).
- Systematic examination of endothelial Rab proteins.
- Assessment of LDL colocalization with Golgi markers (TGN46).
- Functional assays involving Rab protein depletion and overexpression.
Main Results:
- LDL transcytosis occurs directly and indirectly via an intracellular compartment, involving the Golgi apparatus.
- Rab6a and Rab10 are essential for LDL transcytosis, with Rab10 overexpression enhancing it.
- Depletion of Rab10 impairs LDL exocytosis from the Golgi, leading to Golgi expansion.
- Albumin transcytosis and SR-BI/ALK1 expression/localization were unaffected by Rab depletion.
Conclusions:
- Internalized LDL is transported to the Golgi, acting as a reservoir for exocytosis during transcytosis.
- Rab6a and Rab10 are critical regulators of LDL transcytosis, specifically controlling LDL exit from the Golgi.
- These findings reveal novel intracellular pathways governing LDL transport in endothelial cells.
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