Editing Secretion (section)

===Mechanism===
[[Eukaryote|Eukaryotic]] [[Cell (biology)|cells]], including [[human cells]], have a highly [[evolution|evolved]] process of secretion. Proteins [[Protein targeting|targeted]] for the outside are [[protein synthesis|synthesized]] by [[ribosome]]s docked to the rough [[endoplasmic reticulum]] (ER). As they are synthesized, these proteins translocate into the ER [[lumen (anatomy)|lumen]], where they are [[Glycosylation|glycosylated]] and where molecular [[Chaperone (protein)|chaperone]]s aid [[protein folding]]. [[Misfolded proteins]] are usually identified here and retrotranslocated by [[Endoplasmic-reticulum-associated protein degradation|ER-associated degradation]] to the [[cytosol]], where they are degraded by a [[proteasome]]. The [[vesicle (biology)|vesicle]]s containing the properly folded proteins then enter the [[Golgi apparatus]].

In the Golgi apparatus, the glycosylation of the proteins is modified and further [[post-translational modification]]s, including cleavage and functionalization, may occur. The [[proteins]] are then moved into secretory vesicles which travel along the [[cytoskeleton]] to the edge of the cell. More modification can occur in the secretory vesicles (for example [[insulin]] is cleaved from [[proinsulin]] in the secretory vesicles).

Eventually, there is [[vesicle fusion]] with the [[cell membrane]] at porosomes, by a process called [[exocytosis]], dumping its contents out of the cell's environment.<ref name=Anderson>{{cite journal | vauthors = Anderson LL | title = Discovery of the 'porosome'; the universal secretory machinery in cells | journal = Journal of Cellular and Molecular Medicine | volume = 10 | issue = 1 | pages = 126–31 | year = 2006 | pmid = 16563225 | pmc = 3933105 | doi = 10.1111/j.1582-4934.2006.tb00294.x }}</ref>

Strict [[biochemical]] control is maintained over this sequence by usage of a [[pH]] gradient: the pH of the cytosol is 7.4, the ER's pH is 7.0, and the cis-golgi has a pH of 6.5. Secretory vesicles have pHs ranging between 5.0 and 6.0; some secretory vesicles evolve into [[lysosome]]s, which have a pH of 4.8.

====Nonclassical secretion====
There are many proteins like [[FGF1]] (aFGF), [[FGF2]] (bFGF), [[interleukin-1]] (IL1) etc. which do not have a signal sequence. They do not use the classical ER-Golgi pathway. These are secreted through various nonclassical pathways.

At least four nonclassical (unconventional) protein secretion pathways have been described.<ref>{{cite journal | vauthors = Nickel W, Seedorf M | title = Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells | journal = Annual Review of Cell and Developmental Biology | volume = 24 | pages = 287–308 | year = 2008 | pmid = 18590485 | doi = 10.1146/annurev.cellbio.24.110707.175320 }}</ref> They include:
* direct protein translocation across the plasma membrane likely through [[membrane transport protein]]s
* [[bleb (cell biology)|blebbing]]
* lysosomal secretion
* release via exosomes derived from multivesicular bodies
In addition, proteins can be released from cells by mechanical or physiological wounding<ref>{{cite journal| vauthors = McNeil PL, Steinhardt RA | title = Plasma membrane disruption: repair, prevention, adaptation | journal = Annual Review of Cell and Developmental Biology | volume = 19 | pages = 697–731 | year = 2003 | pmid = 14570587 | doi = 10.1146/annurev.cellbio.19.111301.140101 }}</ref> and through non-lethal, transient [[Oncotic pressure|oncotic pores]] in the plasma membrane induced by washing cells with serum-free media or buffers.<ref>{{cite journal | vauthors = Chirico WJ | title = Protein release through nonlethal oncotic pores as an alternative nonclassical secretory pathway | journal = BMC Cell Biology | volume = 12 | pages = 46 | date = October 2011 | pmid = 22008609 | pmc = 3217904 | doi = 10.1186/1471-2121-12-46 | doi-access = free }}</ref>