Unconventional protein secretion

Unconventional protein secretion (known as ER/Golgi-independent protein secretion or nonclassical protein export[1]) represents a manner in which the proteins are delivered to the surface of plasma membrane or extracellular matrix independent of the endoplasmic reticulum or Golgi apparatus.[2] This includes cytokines and mitogens with crucial function in complex processes such as inflammatory response or tumor-induced angiogenesis. Most of these proteins are involved in processes in higher eukaryotes, however an unconventional export mechanism was found in lower eukaryotes too.[3] Even proteins folded in their correct conformation can pass plasma membrane this way, unlike proteins transported via ER/Golgi pathway.[1] Two types of unconventional protein secretion are these: signal-peptid-containing proteins and cytoplasmatic and nuclear proteins that are missing an ER-signal peptide (1).[2]

Signal-peptide-containing proteins

These proteins contain a specific signal-peptide sequence, which is to be translated into the endoplasmic reticulum, but are, however, able to reach the cell surface unconventionally. They can be packed into a COPII-coated vesicle and directly fuse with plasma membrane or can fuse with endosomal or lysosomal compartment. Alternatively, they can be packed into non-COPII-coated vesicle as well and fuse with Golgi (before reaching plasma membrane) or directly delivered to the plasma membrane.[2]

Cytoplasmatic/nuclear secretory proteins

Soluble proteins can reach the surface of the cell both by non-vesicular and vesicular mechanisms. Non-vesicular mechanisms use a carrier to get proteins into extracellular space (for example phosphatidylinositol-4,5-bisphosphate). Vesicular mechanisms can use the lysosome-dependent pathway, microvesicle shedding or biogenesis of multivesicular bodies.[2]

References

1. Backhaus R, Zehe C, Wegehingel S, Kehlenbach A, Schwappach B, Nickel W (April 2004). "Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding". Journal of Cell Science. 117 (Pt 9): 1727–1736. doi:10.1242/jcs.01027. PMID 15075234.
2. Nickel W, Rabouille C (February 2009). "Mechanisms of regulated unconventional protein secretion". Nature Reviews. Molecular Cell Biology. 10 (2): 148–155. doi:10.1038/nrm2617. PMID 19122676. S2CID 9824754.
3. Nickel W (October 2010). "Pathways of unconventional protein secretion". Current Opinion in Biotechnology. 21 (5): 621–626. doi:10.1016/j.copbio.2010.06.004. PMID 20637599.