Glial fibrillary acidic protein

Source: Wikipedia, the free encyclopedia.
GFAP
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000131095

ENSMUSG00000020932

UniProt

P14136

P03995

RefSeq (mRNA)

NM_002055
NM_001131019
NM_001242376
NM_001363846

NM_001131020
NM_010277

RefSeq (protein)

NP_001124491
NP_001229305
NP_002046
NP_001350775

NP_001124492
NP_034407

Location (UCSC)Chr 17: 44.9 – 44.92 MbChr 11: 102.78 – 102.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Glial fibrillary acidic protein (GFAP) is a

fibroblasts taken from rat kidneys,[8] Leydig cells of the testis in both hamsters[9] and humans,[10] human keratinocytes,[11] human osteocytes and chondrocytes[12] and stellate cells of the pancreas and liver in rats.[13]

GFAP is closely related to the other three non-

cell marker. The protein was named and first isolated and characterized by Lawrence F. Eng in 1969.[15] In humans, it is located on the long arm of chromosome 17.[16]

Structure

Type III intermediate filaments contain three domains, named the head, rod and tail domains. The specific

keratins, the type I and II intermediate filaments: in cells that express both proteins, two separate intermediate filament networks form,[18]
which can allow for specialization and increased variability.

To form networks, the initial GFAP dimers combine to make staggered

aromatic residue that have been shown to be required for proper assembly.[20]

Function in the central nervous system

GFAP is expressed in the

blood brain barrier
.

GFAP has been shown to play a role in

myelination, white matter structure deterioration, and functional/structural impairment of the blood–brain barrier.[24] These data suggest that GFAP is necessary for many critical roles in the CNS
.

GFAP is proposed to play a role in

MgCl2 and/or calcium/calmodulin dependent phosphorylation at various serine or threonine residues by PKC and PKA[27] which are two kinases that are important for the cytoplasmic
transduction of signals. These data highlight the importance of GFAP for cell-cell communication.

GFAP has also been shown to be important in repair after CNS injury. More specifically for its role in the formation of glial scars in a multitude of locations throughout the CNS including the eye[28] and brain.[29]

Autoimmune GFAP astrocytopathy

In 2016 a CNS inflammatory disorder associated with anti-GFAP

autoantibodies
.

Meningoencephalitis is the predominant clinical presentation of autoimmune GFAP astrocytopathy in published case series.[30] It also can appear associated with encephalomyelitis and parkinsonism.[31]

Disease states

immunostaining in a glial neoplasm (anaplastic astrocytoma
)
EnCor Biotechnology Inc.

There are multiple disorders associated with improper GFAP regulation, and injury can cause

up-regulation of GFAP.[33]

Another condition directly related to GFAP is

seizures.[34] The cellular mechanism of the disease is the presence of cytoplasmic accumulations containing GFAP and heat shock proteins, known as Rosenthal fibers.[35] Mutations in the coding region of GFAP have been shown to contribute to the accumulation of Rosenthal fibers.[36] Some of these mutations have been proposed to be detrimental to cytoskeleton formation as well as an increase in caspase 3 activity,[37] which would lead to increased apoptosis
of cells with these mutations. GFAP therefore plays an important role in the pathogenesis of Alexander disease.

Notably, the expression of some GFAP

neurodegeneration.[38]
Additionally, reduction in GFAP expression has also been reported in
Down's syndrome, schizophrenia, bipolar disorder and depression.[38]

The generally high abundance of GFAP in the CNS has led to a great interest in GFAP as a blood biomarker of acute injury to the brain and spinal cord in different types of disease mechanisms, such as traumatic brain injury and cerebrovascular disease.[43] Elevated blood levels of GFAP are also found in neuroinflammatory diseases, such as multiple sclerosis and neuromyelitis optica, a disease targeting astrocytes.[43] In a study of 22 child patients undergoing extracorporeal membrane oxygenation (ECMO), children with abnormally high levels of GFAP were 13 times more likely to die and 11 times more likely to suffer brain injury than children with normal GFAP levels.[44]

Interactions

Glial fibrillary acidic protein has been shown to

PSEN1.[46]

Isoforms

Although GFAP alpha is the only isoform which is able to assemble homomerically, GFAP has 8 different

isoforms which label distinct subpopulations of astrocytes in the human and rodent brain. These isoforms include GFAP kappa, GFAP +1 and the currently best researched GFAP delta. GFAP delta appears to be linked with neural stem cells (NSCs) and may be involved in migration. GFAP+1 is an antibody which labels two isoforms. Although GFAP+1 positive astrocytes are supposedly not reactive astrocytes, they have a wide variety of morphologies including processes of up to 0.95mm (seen in the human brain). The expression of GFAP+1 positive astrocytes is linked with old age and the onset of AD pathology.[47]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131095 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020932 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 9693047
    .
  6. ^
    S2CID 10224197
    .
  7. S2CID 38131934
    .
  8. S2CID 31851422
    .
  9. S2CID 3766335
    .
  10. PMID 11993850
    .
  11. PMID 6205529
    .
  12. S2CID 34069861
    .
  13. PMID 9771417
    .
  14. PMID 17555726
    .
  15. S2CID 9221868
    .
  16. PMID 1847665
    .
  17. ^
    PMID 2740350
    .
  18. PMID 1710225
    .
  19. PMID 2745549
    .
  20. PMID 7979242
    .
  21. PMID 24005729
    .
  22. PMID 35765081
    .
  23. PMID 2165732
    .
  24. S2CID 14714870
    .
  25. PMID 1999469
    .
  26. ^ Online Mendelian Inheritance in Man (OMIM): Glial Fibrillary Acidic Protein, GFAP - 137780
  27. S2CID 28248825
    .
  28. PMID 3548695
    .
  29. S2CID 1411700
    .
  30. S2CID 210166834
    .
  31. S2CID 209498996
    .
  32. PMID 13688845
    .
  33. S2CID 25610288
    .
  34. ^ HealthLink (2007-11-25). "Alexander Disease". Medical College of Wisconsin.
  35. PMID 17065456
    .
  36. S2CID 10159452
    .
  37. PMID 21756903
    .
  38. ^
    PMID 10822341
    .
  39. PMID 8974344
    .
  40. PMID 8381971
    .
  41. PMID 7975257
    .
  42. PMID 8381171
    .
  43. ^
    S2CID 246492708
    .
  44. ^ "Protein Found to Predict Brain Injury in Children on ECMO Life Support". Johns Hopkins Children's Center. 19 November 2010. Archived from the original on 9 March 2012. Retrieved 11 December 2010.
  45. PMID 12169273
    .
  46. PMID 12058025
    .
  47. S2CID 41192525
    .

Further reading

External links
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