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Published on: December 29, 2017
Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes
Yong Li1,2, Yiling Wen2, Ying Li3
1Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100084, China.
Abstract:
Migrasomes, vesicular organelles generated on the retraction fibers of migrating cells, play a crucial role in migracytosis, mediating intercellular communication. The cargoes determine the functional specificity of migrasomes. Migrasomes harbor numerous intraluminal vesicles, a pivotal component of their cargoes. The mechanism underlying the transportation of these intraluminal vesicles to the migrasomes remains enigmatic. In this study, we identified that Rab10 and Caveolin-1 (CAV1) mark the intraluminal vesicles in migrasomes. Transport of Rab10-CAV1 vesicles to migrasomes required the motor protein Myosin Va and adaptor proteins RILPL2. Notably, the phosphorylation of Rab10 by the kinase LRRK2 regulated this process. Moreover, CSF-1 can be transported to migrasomes through this mechanism, subsequently fostering monocyte-macrophage differentiation in skin wound healing, which served as a proof of the physiological importance of this transporting mechanism.
Insights
Researchers discovered how intraluminal vesicles, marked by Rab10 and Caveolin-1 (CAV1), are transported to migrasomes. This mechanism, involving Myosin Va, RILPL2, and LRRK2-mediated Rab10 phosphorylation, is vital for cell communication and wound healing.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Migrasomes are key organelles in cell migration and intercellular communication.
- Intraluminal vesicles within migrasomes are crucial cargoes, but their transport mechanism is unknown.
- Understanding migrasome cargo transport is essential for deciphering cell signaling pathways.
Purpose of the Study:
- To elucidate the mechanism of intraluminal vesicle transport to migrasomes.
- To identify the molecular players involved in this transport process.
- To demonstrate the physiological relevance of this transport in wound healing.
Main Methods:
- Utilized immunofluorescence microscopy to visualize Rab10 and Caveolin-1 (CAV1) in migrasomes.
- Employed biochemical assays to study the roles of Myosin Va, RILPL2, and LRRK2.
- Investigated the effect of CSF-1 transport via migrasomes on monocyte-macrophage differentiation.
Main Results:
- Identified Rab10 and CAV1 as markers for intraluminal vesicles within migrasomes.
- Demonstrated that Myosin Va and RILPL2 are essential for transporting these vesicles.
- Showed that LRRK2-mediated phosphorylation of Rab10 regulates the transport process.
- Confirmed CSF-1 transport to migrasomes, promoting monocyte-macrophage differentiation.
Conclusions:
- A novel mechanism for transporting Rab10-CAV1 vesicles to migrasomes has been identified.
- This pathway involves Myosin Va, RILPL2, and LRRK2-regulated Rab10.
- The transport of CSF-1 via migrasomes plays a significant role in skin wound healing and immune cell differentiation.
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