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 to extracellular matrix regardless of ER/Golgi- dependent protein secretion.[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 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 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 plasma membrane.[2]
Cytoplasmatic/nuclear secretory proteins
Soluble proteins can reach the surface of the cell both by non-vesicular and vesicular mechanism. Non-vesicular mechanism use a carrier to get protein into extracellular space (for example phosphatidylinositol-4,5-bisphoshate). Vesicular mechanism can use lysosome-dependent pathway, microvesicle shedding or biogenesis of multivesicular bodies.[2]
References
- 1 2 Backhaus, R; Zehe, C; Wegehingel, S; Kehlenbach, A; Schwappach, B; Nickel, W (Apr 1, 2004). "Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding.". Journal of Cell Science 117 (Pt 9): 1727–36. doi:10.1242/jcs.01027. PMID 15075234.
- 1 2 3 4 Nickel, W; Rabouille, C (Feb 2009). "Mechanisms of regulated unconventional protein secretion.". Nature reviews. Molecular cell biology 10 (2): 148–55. doi:10.1038/nrm2617. PMID 19122676.
- ↑ Nickel, W (Oct 2010). "Pathways of unconventional protein secretion.". Current opinion in biotechnology 21 (5): 621–6. doi:10.1016/j.copbio.2010.06.004. PMID 20637599.