Activity-regulated cytoskeleton-associated protein

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(Redirected from
Arc/Arg3.1
)
ARC
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000198576

ENSMUSG00000022602

UniProt

Q7LC44

Q9WV31

RefSeq (mRNA)

NM_015193

NM_001276684
NM_018790

RefSeq (protein)

NP_056008

NP_001263613
NP_061260

Location (UCSC)Chr 8: 142.61 – 142.61 MbChr 15: 74.54 – 74.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Activity-regulated cytoskeleton-associated protein is a plasticity protein that in humans is encoded by the ARC gene. The gene is believed to derive from a retrotransposon.[5] The protein is found in the neurons of tetrapods and other animals where it can form virus-like capsids that transport RNA between neurons.[5]

ARC

translated protein is believed to play a critical role in learning and memory-related molecular processes.[8] Arc protein is widely considered to be important in neurobiology because of its activity regulation, localization, and utility as a marker for plastic changes in the brain. Dysfunction in the production of Arc protein has been implicated as an important factor in understanding various neurological conditions, including amnesia,[9] Alzheimer's disease, Autism spectrum disorders, and Fragile X syndrome.[10]

ARC was first characterized in 1995

fluorescent in situ hybridization
).

Gene

The ARC gene, located on

myocyte enhancer factor 2 (MEF2), and SRF.[20]

The

heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2).[24]

It is suspected that the ARC gene originated from the

Ty3/gypsy retrotransposon and was repurposed for mediating neuron-neuron communication.[5]

Trafficking

Following transcription, Arc mRNA is transported out of the nucleus and localized to neuronal dendrites

polyribosomes at synaptic sites,[29] and is translated in isolated synaptoneurosomal fractions in vitro[30]
indicating that the protein is likely locally translated in vivo.

Protein

Once transported, the translated protein is 396 residues in length, with an

capsids that package mRNA and can traffic between cells.[34][5]

Synaptically localized Arc protein interacts with dynamin and endophilin, proteins involved in clathrin-mediated endocytosis, and facilitates the removal of AMPA receptors from the plasma membrane.[32] Consistent with this, increased Arc levels reduce AMPA currents,[35] while Arc KOs display increases in surface AMPA expression.[36]

Knockouts

Arc is critical as a ubiquitous signaling factor in early embryonic development and is required for growth and patterning during

homozygous knockout mice by targeting the entire Arc gene rather than portions of the coding region, eliminating dominant negative effects. These animals proved viable and exhibit no gross malformations in neuronal architecture, but express higher levels of the GluR1 subunit and increased miniature excitatory postsynaptic currents (mEPSCs) in addition to displaying deficiencies in long-term memory.[38]

Signaling

The Arc transcript is dependent upon activation of the

H89, a PKA antagonist, blocks these effects[41] as does further downstream blockade of mitogen-activated protein kinase kinase [sic] (MEK).[18] Note that the MAPK cascade is a signaling pathway involving multiple kinases
acting sequentially [MAPKKK→ MAPKK→ MAPK].

MAPK is able to enter the nucleus and perform its phosphotransferase activity on a number of gene regulatory components

zif268.[44]

Behavioral effects

Changes in Arc mRNA and/or protein are correlated with a number of behavioral changes including cued fear conditioning,[45] contextual fear conditioning,[46] spatial memory,[47][48] operant conditioning,[49][50] and inhibitory avoidance.[8] The mRNA is notably upregulated following electrical stimulation in LTP-induction procedures such as high frequency stimulation (HFS),[47] and is massively and globally induced by maximal electroconvulsive shock (MECS).[11][6]

Arc in insects

It has been found that Arc may have been acquired by animals more than once. While Arc seems to be closely related among all

silkworms (Bombyx mori), and Argentine ants (Linepithema humile) may have been transferred to a common ancestor of these insects by another event.[51][52][53]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000198576 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022602 – 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 29570995
    .
  6. ^
    PMID 9412483
    .
  7. ^
    S2CID 13395819
    .
  8. ^
    PMID 16020527
    .
  9. S2CID 26622850
    .
  10. ^ "Arc protein 'could be key to memory loss', says study". BBC News Online. 2013-06-09. Retrieved 2013-06-09.
  11. ^
    S2CID 18117517
    .
  12. S2CID 15647476
    .
  13. PMID 12451105
    .
  14. ^ "Gene: Arc (ENSMUSG00000022602) - Summary - Mus musculus - Ensembl genome browser 100".
  15. ^ "Gene: Arc (ENSRNOG00000043465) - Summary - Rattus norvegicus - Ensembl genome browser 100".
  16. ^ "Gene: ARC (ENSG00000198576) - Summary - Homo sapiens - Ensembl genome browser 100".
  17. ^
    PMID 11466419
    .
  18. ^
    PMID 19193899
    .
  19. ^
    PMID 19116276
    .
  20. ^
    S2CID 8091392
    .
  21. ^
    S2CID 14840114
    .
  22. PMID 15145352
    .
  23. PMID 18305102
    .
  24. S2CID 15824001
    .
  25. ^
    PMID 17715342
    .
  26. S2CID 14770642
    .
  27. S2CID 604555
    .
  28. PMID 10783400
    .
  29. PMID 11842217
    .
  30. S2CID 17577498
    .
  31. ^
    PMID 17088211
    .
  32. S2CID 6439070
    .
  33. PMID 29328915
    .
  34. PMID 17088212
    .
  35. PMID 17088213
    .
  36. S2CID 1274133
    .
  37. S2CID 2039086
    .
  38. S2CID 14011921
    .
  39. PMID 17395606
    .
  40. ^
    PMID 17981809
    .
  41. S2CID 21888831
    .
  42. PMID 8791420
    .
  43. PMID 16287845
    .
  44. PMID 15988467
    .
  45. PMID 16452685
    .
  46. ^
    PMID 10818134
    .
  47. PMID 11438584
    .
  48. S2CID 12146147
    .
  49. PMID 12878684
    .
  50. ^ Letzter R (2 February 2018). "An Ancient Virus May Be Responsible for Human Consciousness". Live Science.
  51. PMID 29328922
    .
  52. PMID 29328916
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Activity-regulated_cytoskeleton-associated_protein&oldid=1217460646"