exocyst

The exocyst is an octameric protein complex involved in vesicle trafficking, specifically the tethering and spatial targeting of post-Golgi vesicles to the plasma membrane prior to vesicle fusion. It is implicated in a number of cell processes, including exocytosis, cell migration, and growth.

Subunits

The exocyst is composed of eight subunits, whose nomenclature differs between mammalian cells and Saccharomyces cerevisiae.

class="wikitable"

!Subunit

!Mammalian cells

!Saccharomyces cerevisiae

1

|EXOC1

|Sec3

2

|EXOC2

|Sec5

3

|EXOC3

|Sec6

4

|EXOC4

|Sec8

5

|EXOC5

|Sec10

6

|EXOC6

|Sec15

7

|EXOC7

|Exo70

8

|EXOC8

|Exo84

Function

The exocyst complex serves to direct vesicles after the Golgi complex to specific locations on the plasma membrane and to mediate their tethering and localization to the membrane immediately before fusion. The exocyst complex has also been implicated in the active trafficking of mitochondria from immune cells to cancer cells. {{cite journal | vauthors = Saha T, Dash C, Jayabalan R, etal | title = Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells. | journal = Nat. Nanotechnol. | date = 2021 | volume = 17 | issue = 1 | pages = 98–106 | doi = 10.1038/s41565-021-01000-4 | pmid = 34795441 | pmc = 10071558 }} Because of this function, the exocyst complex is heavily involved in exocytosis. Sec3 (EXOC1) and Exo70 (EXOC7) are localized to the plasma membrane, and are physically attached to the membrane by Rho GTPases such as CDC42. Other complementary exocyst components such as Sec15 (EXOC6) and Sec4 are localized to the vesicle membrane. Exocyst proteins on the plasma membrane bind vesicular exocyst proteins, bringing the vesicle very close to the plasma membrane in a fashion similar to the SNARE interactions to facilitate fusion.

The exocyst also interacts with Rho GTPases responsible for controlling cell polarity and the activity of the cytoskeleton.

History

Hints of a multi-subunit complex involved in yeast exocytosis came from work in Peter Novick's group, then at Yale University School of Medicine, in the early 1990s.{{cite journal |vauthors=Hsu SC, TerBush D, Abraham M, Guo W |title=The exocyst complex in polarized exocytosis |journal=Int Rev Cytol |series=International Review of Cytology |volume=233 |issue= |pages=243–65 |date=2004 |pmid=15037366 |doi=10.1016/S0074-7696(04)33006-8|isbn=978-0-12-364637-8 }} Works led by Robert Bowser and Daniel TerBush in 1992 and 1995 respectively isolated Sec6p and Sec8p, showing them to participate in a complex of at least eight proteins, found at the site of active exocytosis.{{cite journal |vauthors=Bowser R, Müller H, Govindan B, Novick P |title=Sec8p and Sec15p are components of a plasma membrane-associated 19.5S particle that may function downstream of Sec4p to control exocytosis |journal=J Cell Biol |volume=118 |issue=5 |pages=1041–56 |date=September 1992 |pmid=1512289 |pmc=2289594 |doi=10.1083/jcb.118.5.1041 }}{{cite journal |vauthors=TerBush DR, Novick P |title=Sec6, Sec8, and Sec15 are components of a multisubunit complex which localizes to small bud tips in Saccharomyces cerevisiae |journal=J Cell Biol |volume=130 |issue=2 |pages=299–312 |date=July 1995 |pmid=7615633 |pmc=2199927 |doi=10.1083/jcb.130.2.299 |url=}} In 1996, the same group identified the exocyst member proteins in yeast and coined the name "exocyst" for the complex.{{cite journal |vauthors=TerBush DR, Maurice T, Roth D, Novick P |title=The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae |journal=EMBO J |volume=15 |issue=23 |pages=6483–94 |date=December 1996 |pmid=8978675 |pmc=452473 |doi= 10.1002/j.1460-2075.1996.tb01039.x}}

References

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