Related Experiment Video
Updated: Mar 12, 2026
08:55
Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
Published on: December 14, 2017
16.2K
Intracellular Localization of PD-L1 in Rab10-positive Open Tubular Endosome System of Cancer Cells.
Risa Yamada1, Rentaro Sakamoto1, Katsuhisa Kawai1
1Department of Histology and Cell Biology, School of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan.
Acta Histochemica Et Cytochemica
|March 11, 2026
Summary
Programmed cell Death-Ligand 1 (PD-L1) recycles to cancer cell surfaces via a Rab10-dependent pathway. This pathway may act as an intracellular reservoir, influencing PD-L1 levels and immune evasion strategies.
Area of Science:
- Cell Biology
- Immunology
- Cancer Research
Background:
- Cancer cells evade immune surveillance by upregulating Programmed cell Death-Ligand 1 (PD-L1) on their surface, which binds to PD-1 on T cells.
- PD-L1 is a critical target for cancer immunotherapy, but its intracellular trafficking remains unclear.
- Rab10, a small GTPase, is involved in a unique endocytic pathway that bypasses lysosomal degradation.
Purpose of the Study:
- To investigate the intracellular trafficking pathway of PD-L1 in cancer cells.
- To determine the role of Rab10 in the regulation of cell surface PD-L1 levels.
Main Methods:
- Live-cell imaging using GFP-PD-L1 and mScarlet-Rab10 fusion proteins.
- Analysis of PD-L1 localization in Rab10-knockout cells.
- Treatment with a PD-L1 inhibitor (BMS-202) to assess trafficking changes.
Main Results:
- PD-L1 was observed to localize within Rab10-positive endocytic tubules in certain cancer cells.
- Rab10-dependent tubular structures were essential for PD-L1 localization, as they were absent in Rab10-knockout cells.
- Inhibition of PD-L1 led to its removal from the cell surface and Rab10-positive endosomes, followed by lysosomal degradation.
Conclusions:
- The Rab10-dependent tubular endocytic pathway serves as an intracellular reservoir for PD-L1.
- This pathway facilitates the recycling of PD-L1 to the cancer cell surface.
- Regulation of this pathway could impact the amount of PD-L1 on cancer cells, influencing immune evasion.
More Related Videos
Related Concept Videos
01:28The Early Endosome: Endocytosis of Transferrin
5.0K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
5.0K
03:03mTOR Signaling and Cancer Progression
5.0K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.0K
01:25Rab Cascades
3.7K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
3.7K
00:58Recycling Endosomes and Transcytosis
3.7K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
3.7K
01:14Rab Proteins
5.3K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.3K
01:35Cancer Cell Migration through Invadopodia
3.4K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.4K