Follistatin
5801035
194347059
2008-02-27T04:21:52Z
Arcadian
104523
/* Clinical significance */ ref format
{{Protbox
|Name=Follistatin
|Photo=Follistatin activin Complex.png
|Caption='''The Structure Of The Follistatin:Activin Complex'''
|Gene = [[HUGO]] code:[http://www.gene.ucl.ac.uk/nomenclature/data/get_data.php?hgnc_id=HGNC:3971 FST]
|Structure =[http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?form=6&db=t&Dopt=s&uid=35669 Follistatin:Activin Complex structure]
|Review =
|Type=[[Growth factor]]
|Functions= Regulates members of the TGF beta superfamily ligands
|Domains= 3 [[FOLN domain]]s, 3 [[KAZAL domain]]s
|Diseases=[[polycystic ovary syndrome]] (PCOS)
|Taxa = ''[[Homo Sapiens]]''; homologs: many [[metazoan]] [[phylum (biology)|phyla]]
| Cells = many, [[placenta]], [[blood]], [[ovary]], [[liver]], [[testis]]
| Location = [[extracellular]]
|Mods=
|Names= '''Follistatin, FSH-Suppressing Protein, Activin-binding protein'''
|Interactions=[[Activin]], [[inhibin]], [[BMP5]]
|Pages=
}}
'''Follistatin''' is a single chain [[autocrine]] glyco[[protein]] found to be ''ubiquitous'' within the body of nearly all higher animals, that is the product of a single [[gene]].
It was initially isolated from '''''follicular fluid''''' and was identified as a protein fraction that inhibited [[Follicle-stimulating hormone]] ('''FSH''') secretion from the [[anterior pituitary]], and so was known as '''''FSH-suppressing protein''''' ('''FSP'''). Since then its primary function has been determined to be the binding and '''''bioneutralization''''' agent of members of the '''TGF-beta superfamily''', with primary focus on [[Activin]], a [[paracrine]] hormone (TGF-b member) which enhances secretion of FSH in the anterior pituitary.
==Biochemistry==
It is part of the inhibin-activin-follistatin axis.
There are three known isoforms, FS-288, FS-300, and FS-315. Two are known to be created by '''[[alternative splicing]]''' of the primary mRNA transcript, FS-288 and FS-315. FS-300 (porcine follistatin) is thought to be the product of '''''post-translational''''' modification via truncation of the primary amino-acid chain.
Although FS is ''ubiquitous'' it's highest concentration has been found to be in the female ovary, followed by the skin.
In the tissues activin has a strong role in '''''cellular proliferation''''', thereby making follistatin the safeguard against uncontrolled cellular proliferation and also allowing it to function as an instrument of '''''cellular differentiation'''''. Both of these roles are vital in tissue rebuilding and repair, and may account for follistatin's high presence in the skin.
In the blood, activin and follistatin are both known to be involved in the '''''inflammatory response''''' following tissue injury or pathogenic incursion. The source of follistatin in circulating blood plasma has yet to be determined, but due to its [[autocrine]] nature speculation suggests the ''endothelial cells'' lining all blood vessels, or the [[macrophage]]s and [[monocytes]] also circulating within the whole blood.
Follistatin is involved in the development of the embryo. It has inhibitory action on bone morphogenic proteins (BMPs); BMPs induce the ectoderm to become epidermal ectoderm. Inhibition of BMPs allows neuroectoderm to arise from ectoderm, a process which eventually forms the neural plate. Other inhibitors involved in this process are noggin and chordin.
Follistatin and BMPs are also known to play a role in [[folliculogenesis]] within the ovary. The main role of follistatin in the oestrus/menstrus ovary, so far, appears to be progression of the follicle from ''early antral'' to ''antral/dominant'', and importantly the promotion of '''cellular differentiation''' of the ''oestrogen'' producing ''granulosa cells'' (GC) of the dominant follicle into the [[progesterone]] producing ''large lutein cells'' (LLC) of the [[corpus luteum]].
{|{{protein
| Name =
| caption =
| image =
| width =
| HGNCid = 3971
| Symbol = FS/FST/FSP
| AltSymbols =
| EntrezGene = 10468
| OMIM = 136470
| RefSeq = NM_013409
| UniProt = P19883
| PDB =
| ECnumber =
| Chromosome = 5
| Arm = q
| Band = 11.2
| LocusSupplementaryData =
}}
|}
==Clinical significance==
Follistatin is being studied for its role in regulation of muscle growth in mice, as an antagonist to '''[[myostatin]]''' (aka '''GDF-8''', a TGF superfamily member) which ''inhibits'' excessive muscle growth. Lee & McPheron demonstrated that inhibitin GDF-8 either by genetic elimination ([[knockout mice]]) or by increasing the amount of follistatin that muscle mass was greatly increased. <ref name="pmid11459935">{{cite journal |author=Lee SJ, McPherron AC |title=Regulation of myostatin activity and muscle growth |journal=[[Proc. Natl. Acad. Sci. U.S.A.]] |volume=98 |issue=16 |pages=9306–11 |year=2001 |pmid=11459935 |doi=10.1073/pnas.151270098 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=11459935}}</ref><ref name="titleMighty mice made mightier">{{cite web |url=http://www.eurekalert.org/pub_releases/2007-08/jhmi-mm082407.php |title='Mighty mice' made mightier |accessdate=2008-02-26 |format= |work=}}</ref>
And is also being investigated for its involvement in [[polycystic ovary syndrome]] ('''PCOS'''), though there is debate as to its direct role in this infertility disease.
==References==
{{reflist}}
==External links==
* {{MeshName|Follistatin}}
{{TGF beta signaling}}
{{Carrier proteins}}
{{molecular-cell-biology-stub}}
[[Category:Proteins]]
[[Category:FOLN domain]]
[[Category:KAZAL domain]]
[[de:Follistatin]]
[[fr:Follistatine]]