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Unconventional protein secretion (known as ER/Golgi-independent protein secretion or nonclassical protein export) represents a manner in which the proteins are delivered to the surface of
plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
or
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
independent of the
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
or
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...
. This includes
cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
and
mitogens A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The cell cycle Mitogens ac ...
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 The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...
, however an unconventional export mechanism was found in lower eukaryotes too. Even proteins folded in their correct conformation can pass plasma membrane this way, unlike proteins transported via ER/Golgi pathway. 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).


Signal-peptide-containing proteins

These proteins contain a specific signal-peptide sequence, which is to be translated into the
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
, 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.


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 Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane ...
.


References

{{Reflist Cell biology Immunology