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Published on: January 16, 2018
The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium
S M Niedziółka1,2, S Datta1, T Uśpieński1,2
1Centre of New Technologies, University of Warsaw, Warsaw, Poland.
Abstract:
The efficient transport of proteins into the primary cilium is a crucial step for many signaling pathways. Dysfunction of this process can lead to the disruption of signaling cascades or cilium assembly, resulting in developmental disorders and cancer. Previous studies on the protein delivery to the cilium were mostly focused on the membrane-embedded receptors. In contrast, how soluble proteins are delivered into the cilium is poorly understood. In our work, we identify the exocyst complex as a key player in the ciliary trafficking of soluble Gli transcription factors. In line with the known function of the exocyst in intracellular vesicle transport, we demonstrate that soluble proteins, including Gli2/3 and Lkb1, can use the endosome recycling machinery for their delivery to the primary cilium. Finally, we identify GTPases: Rab14, Rab18, Rab23, and Arf4 that are involved in vesicle-mediated Gli protein ciliary trafficking. Our data pave the way for a better understanding of ciliary transport and uncover transport mechanisms inside the cell.
Insights
The exocyst complex facilitates soluble protein transport into primary cilia via endosome recycling. This study identifies key GTPases involved in trafficking crucial for cell signaling and development.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Efficient protein transport into primary cilia is vital for signaling pathways.
- Cilium dysfunction is linked to developmental disorders and cancer.
- Mechanisms for soluble protein ciliary import remain largely unknown.
Purpose of the Study:
- To investigate the mechanisms of soluble protein transport into primary cilia.
- To identify key protein complexes and GTPases involved in this process.
Main Methods:
- Utilized genetic and cell biological approaches.
- Investigated the role of the exocyst complex in ciliary trafficking.
- Analyzed the involvement of endosome recycling machinery and specific GTPases.
Main Results:
- Identified the exocyst complex as essential for ciliary trafficking of soluble Gli transcription factors.
- Demonstrated that soluble proteins use endosome recycling pathways for ciliary import.
- Pinpointed Rab14, Rab18, Rab23, and Arf4 as critical GTPases in vesicle-mediated Gli transport.
Conclusions:
- The exocyst complex and endosome recycling machinery mediate soluble protein import into primary cilia.
- Specific GTPases regulate vesicle-mediated transport of Gli proteins to cilia.
- These findings enhance understanding of ciliary transport and intracellular mechanisms.
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