Английская Википедия:GRIK1

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Шаблон:Short description Шаблон:Infobox gene Glutamate receptor, ionotropic, kainate 1, also known as GRIK1, is a protein that in humans is encoded by the GRIK1 gene.[1]

Function

This gene encodes one of the many ionotropic glutamate receptor (GluR) subunits that function as a ligand-gated ion channel. The specific GluR subunit encoded by this gene is of the kainate receptor subtype. Receptor assembly and intracellular trafficking of ionotropic glutamate receptors are regulated by RNA editing and alternative splicing. These receptors mediate excitatory neurotransmission and are critical for normal synaptic function. Two alternatively spliced transcript variants that encode different isoforms have been described. Exons of this gene are interspersed with exons from the C21orf41 gene, which is transcribed in the same orientation as this gene but does not seem to encode a protein.[1]

Interactions

GRIK1 has been shown to interact with DLG4,[2] PICK1[2] and SDCBP.[2]

RNA editing

Type

A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3, with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues, whereas ADAR3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site, with residues usually in a neighboring intron, but can be an exonic sequence. The region that base-pairs with the editing region is known as an Editing Complementary Sequence (ECS). ADARs bind interact directly with the dsRNA substrate via their double-stranded RNA binding domains. If an editing site occurs within a coding sequence, the result could be a codon change. This can lead to translation of a protein isoform due to a change in its primary protein structure. Therefore, editing can also alter protein function. A to I editing occurs in a noncoding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs( especially Alu repeats). The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus, among others.

Location

The pre-mRNA of GluR-5 is edited at one position at the Q/R site located at membrane region 2 (M2). There is a codon change as a result of editing. The codon change is (CAG) Glutamine (Q) to (CGG) an Arginine (R).[3] Like GluR-6 the ECS is located about 2000 nucleotides downstream of the editing site.[4]

Regulation

Editing of the Q/R site is development- and tissue-regulated. Editing in the spinal cord, corpus callosum, cerebellum is 50%, while editing in the Thalamus, amygdala, hippocampus is about 70%.

Consequences

Structure

Editing results in a change in amino acid in the second membrane domain of the receptor.

Function

The editing site is found within the second intracellular domain. It is thought that editing affects the permeability of the receptor to CA2+. Editing of the Q/R site is thought to reduce the permeability of the channel to Ca2+[3]

RNA editing of the Q/R site can effect inhibition of the channel by membrane fatty acids such as arachidonic acid and docosahexaenoic acid[5] For Kainate receptors with only edited isoforms, these are strongly inhibited by these fatty acids. However, inclusion of just one nonedited subunit is enough to stop this inhibition(.[5]

See also

References

Шаблон:Reflist

Further reading

Шаблон:Refbegin

Шаблон:Refend Шаблон:PDB Gallery

External links

Шаблон:NLM content Шаблон:Ligand-gated ion channels

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  1. ↑ 1,0 1,1 Шаблон:Cite web
  2. ↑ 2,0 2,1 2,2 Шаблон:Cite journal
  3. ↑ 3,0 3,1 Шаблон:Cite journal
  4. ↑ Шаблон:Cite journal
  5. ↑ 5,0 5,1 Шаблон:Cite journal
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