Follistatin

FST
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3HH2, 2B0U, 2P6A
Identifiers
Aliases	FST, FS, follistatin
External IDs	OMIM: 136470 MGI: 95586 HomoloGene: 7324 GeneCards: FST
Gene ontology Molecular function • heparan sulfate proteoglycan binding • protein binding • signal transducer activity • activin binding Cellular component • extracellular region Biological process • positive regulation of hair follicle development • negative regulation of activin receptor signaling pathway • negative regulation of transcription from RNA polymerase II promoter • hematopoietic progenitor cell differentiation • signal transduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10468	14313
Ensembl	ENSG00000134363	ENSMUSG00000021765
UniProt	P19883	P47931
RefSeq (mRNA)	NM_006350 NM_013409	NM_008046 NM_001301373 NM_001301375
RefSeq (protein)	NP_006341.1 NP_037541.1	NP_001288302.1 NP_001288304.1 NP_032072.1
Location (UCSC)	Chr 5: 53.48 – 53.49 Mb	Chr 13: 114.45 – 114.46 Mb
PubMed search	[1]	[2]
Wikidata

Follistatin also known as activin-binding protein is a protein that in humans is encoded by the FST gene.^[3][4] Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals.^[4]

Its primary function is the binding and bioneutralization of members of the TGF-β superfamily, with a particular focus on activin, a paracrine hormone.

An earlier name for the same protein was FSH-suppressing protein (FSP). At the time of its initial isolation from follicular fluid, it was found to inhibit the anterior pituitary's secretion of follicle-stimulating hormone (FSH).

Biochemistry

Follistatin is part of the inhibin-activin-follistatin axis.

Currently there are three reported isoforms, FS-288, FS-300, and FS-315. Two, FS-288 and FS-315, are known to be created by alternative splicing of the primary mRNA transcript. FS-300 (porcine follistatin) is thought to be the product of posttranslational modification via truncation of the C-terminal domain from the primary amino-acid chain.

Although FS is ubiquitous its highest concentration has been found to be in the female ovary, followed by the skin.

The activin-binding protein follistatin is produced by folliculostellate (FS) cells of the anterior pituitary. FS cells make numerous contacts with the classical endocrine cells of the anterior pituitary including gonadotrophs.

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 macrophages and monocytes also circulating within the whole blood, may be sources.

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 estrogen producing granulosa cells (GC) of the dominant follicle into the progesterone producing large lutein cells (LLC) of the corpus luteum.

Clinical significance

Follistatin is being studied for its role in regulation of muscle growth in mice, as an antagonist to myostatin (also known as GDF-8, a TGF superfamily member) which inhibits excessive muscle growth. Lee & McPherron demonstrated that inhibition of GDF-8, either by genetic elimination (knockout mice) or by increasing the amount of follistatin, resulted in greatly increased muscle mass.^[5][6] In 2009, research with macaque monkeys demonstrated that regulating follistatin via gene therapy also resulted in muscle growth and increases in strength. This research paves the way for human clinical trials, which are hoped to begin in the summer of 2010 on Inclusion body myositis.^[7]

A study has also shown that increased levels of follistatin, by leading to increased muscle mass of certain core muscular groups, can increase life expectancy in cases of spinal muscular atrophy (SMA) in animal models.^[8]

It 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

Further reading

External links

• Follistatin at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery
1lr8: Crystal structure of Fs1, the heparin-binding domain of follistatin, complexed with the heparin analogue D-myo-inositol hexasulphate (Ins6S)  2p6a: The structure of the Activin:Follistatin 315 complex  1lr7: Crystal structure of Fs1, the heparin-binding domain of follistatin, complexed with the heparin analogue sucrose octasulphate (SOS)  2arp: Activin A in complex with Fs12 fragment of follistatin  1lr9: STRUCTURE OF Fs1, THE HEPARIN-BINDING DOMAIN OF FOLLISTATIN  2b0u: The Structure of the Follistatin:Activin Complex