The unique structural and functional features of CXCL12.
Rik Janssens1, Sofie Struyf1, Paul Proost2
1Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, KU Leuven, University of Leuven, B-3000, Leuven, Belgium.
Cellular & Molecular Immunology
|October 31, 2017
Summary
The chemokine CXCL12 regulates cell migration in development and disease. Its activity is controlled by splice variants, receptor interactions, and post-translational modifications, ensuring precise biological functions.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CXC chemokine CXCL12 is crucial for embryogenesis, hematopoiesis, angiogenesis, and inflammation.
- It mediates the migration of hematopoietic stem cells, endothelial cells, and leukocytes.
- CXCL12 activity is tightly regulated through various mechanisms.
Purpose of the Study:
- To review the interactions of CXCL12 with its cellular environment.
- To discuss the diverse regulatory mechanisms controlling CXCL12 activity.
Main Methods:
- Review of existing literature on CXCL12.
- Analysis of CXCL12 splice variants, receptor interactions (CXCR4, ACKR3), and glycosaminoglycan binding.
- Examination of post-translational modifications impacting CXCL12 function.
Main Results:
- CXCL12 exists in six human splice variants with distinct tissue distribution and activity.
- CXCL12 interacts with CXCR4 and ACKR3, and binds to GAGs for leukocyte presentation.
- Post-translational modifications like citrullination and nitration reduce CXCL12 activity.
Conclusions:
- CXCL12 activity is precisely controlled at multiple levels, including transcription, mRNA stability, receptor binding, and post-translational modifications.
- Understanding these regulatory mechanisms is key to comprehending CXCL12's role in physiological and pathological processes.
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