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Protein Reviews pp 93–101Cite as

Regulation of the Extracellular SERPINA5 (Protein C Inhibitor) Penetration Through Cellular Membranes

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Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 966))

Abstract

It is generally accepted that the phospholipid bilayer of the cell membrane is impermeable for proteins and peptides and that these molecules require special mechanisms for their transport from the extra- to the intracellular space. Recently there is increasing evidence that certain proteins/peptides can also directly cross the phospholipid membrane. SERPINA5 (protein C inhibitor) is a secreted protease inhibitor with broad protease reactivity and wide tissue distribution. It binds glycosaminoglycans and certain phospoholipids, which can modulate its inhibitory activity. SERPINA5 has been shown to be internalized by platelets, granulocytes, HL-60 promyelocytic leukemia cells, and by Jurkat lymphoma cells. Once inside the cell it can translocate to the nucleus. There are several indications that SERPINA5 can directly cross the phospholipid bilayer of the cell membrane. In this review we will describe what is known so far about the conditions, as well as the cellular and molecular requirements for SERPINA5 translocation through the cell membrane and for its penetration of pure phospholipid vesicles.

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Abbreviations

LRP:

LDL-receptor related protein, alpha-2-macroglobulin receptor

LUV:

large unilamellar vesicle

PCI:

protein C inhibitor

PE:

phosphatidylethanolamine

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Acknowledgements

This work was supported by grants P22792-B11 from the Austrian Science Fund (FWF) and 14064 from the “Medizinisch-wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien” (both to MG).

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria

    Felix C. Wahlmüller, Hanjiang Yang, Margareta Furtmüller & Margarethe Geiger

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  1. Felix C. Wahlmüller
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  2. Hanjiang Yang
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  3. Margareta Furtmüller
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  4. Margarethe Geiger
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Correspondence to Margarethe Geiger .

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  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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Wahlmüller, F.C., Yang, H., Furtmüller, M., Geiger, M. (2017). Regulation of the Extracellular SERPINA5 (Protein C Inhibitor) Penetration Through Cellular Membranes. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 966. Springer, Singapore. https://doi.org/10.1007/5584_2017_60

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