Pikachurin

Pikachurin is an extracellular matrix-like retinal protein first discovered in 2008 in Japan by Shigeru Sato et al. and named after Pikachu, a species of the Pokémon franchise.{{cite web |title=Researchers: 'Pikachurin' protein linked with kinetic vision |url=http://www.yomiuri.co.jp/dy/features/science/20080722TDY02306.htm |website=Daily Yomiuri Online |publisher=The Daily Yomiuri |archive-url=https://web.archive.org/web/20080727140433/http://www.yomiuri.co.jp/dy/features/science/20080722TDY02306.htm |archive-date=27 July 2008 |language=en |date=22 July 2008}} The name of this protein was inspired by Pikachu's "lightning-fast moves".

Pikachurin was initially identified in a microarray analysis of gene expression profiles of the retinas of wild-type and Otx2 knockout mice. A RT-PCR analysis was used to confirm that Otx2 regulates the expression of pikachurin, it was known because there was an absence of expression of pikachurin in the Otx2 mice retina, so it indicates that Otx2 regulates pikachurin. The localization of pikachurin to synaptic cleft in the photoreceptor ribbon synapse was determined using fluorescent antibodies. Tissue targeting of gene disruption of pikachurin was used to determine that this protein is necessary for proper synaptic signal transmission and visual function. α-dystroglycan was shown to interact with pikachurin through immunoprecipitation.

Dystroglycan ligand with other proteins is essential. Glycosylation of dystroglycan is necessary for its ligand binding activity. Mutations in glycosyltransferase enzymes cause abnormal glycosylation of dystroglycan. This hypoglycosylation is associated with less binding with other proteins and causes some congenital muscular dystrophy. Pikachurin is the most recently identified dystroglycan ligand protein and is localized in the synaptic cleft in the photoreceptor ribbon synapse. The binding between dystroglycan and pikachurin requires divalent cations. Ca²⁺ produces strongest binding; Mn²⁺ produces only faint bindings and no binding with Mg²⁺ alone. Dystroglycan has different domains that allow multiple Ca²⁺ sites to form a stable pikachurin-dystroglycan connection. This shows that pikachurin can form oligomeric structures; and suggests the possibility of clustering effects can be important in modulating pikachurin-dystroglycan interactions.

Another thing to be considered is that the presence of NaCl (0.5M) strongly inhibits interaction between DG and other ligand proteins but has a modest inhibitory effect with pikachurin-DG ligand. This shows that there are differences between the binding of pikachurin-DG binding and DG binding with other proteins.

Pikachurin seems to have more domains to bind with DG than other proteins. For example, experiments in ligand competition shows that presence of pikachurin inhibits laminin-111 binding with DG, but high concentrations of laminin-111 do not inhibit pikachurin binding to DG.

Image:Pikachurin.jpg

The protein is colocalized with both dystrophin and dystroglycan at the ribbon synapses.

Pikachurin, along with laminin, perlecan, agrin, neurexin, binds to α-dystroglycan in the extracellular space. As such, pikachurin, as well as the other previously-mentioned proteins, is necessary for the proper functioning of dystroglycan. Pikachurin is necessary for the apposition of presynaptic and postsynaptic termini in the ribbon synapse; deletion of pikachurin causes an abnormal electroretinogram, similarly to the deletion of nestin.{{cite journal | vauthors = Satz JS, Philp AR, Nguyen H, Kusano H, Lee J, Turk R, Riker MJ, Hernández J, Weiss RM, Anderson MG, Mullins RF, Moore SA, Stone EM, Campbell KP | title = Visual impairment in the absence of dystroglycan | journal = The Journal of Neuroscience | volume = 29 | issue = 42 | pages = 13136–46 | date = October 2009 | pmid = 19846701 | pmc = 2965532 | doi = 10.1523/JNEUROSCI.0474-09.2009 }}

File:Ribbon Synapse.png

Synapse formation is crucial for the mammalian CNS (central nervous system) to function correctly. Retinal photoreceptors finish at the axon terminal which forms a specialized structure, the ribbon synapse, which specifically connects photoreceptor synaptic terminals with bipolar and horizontal cell terminals in the outer plexiform layer (OPL) of the retina.

It is clear that Pikachurin, an extracellular matrix–like retinal protein, is localized to the synaptic cleft in the photoreceptor ribbon synapse.{{cite journal | vauthors = Satz JS, Campbell KP | title = Unraveling the ribbon synapse | journal = Nature Neuroscience | volume = 11 | issue = 8 | pages = 857–9 | date = August 2008 | pmid = 18660835 | doi = 10.1038/nn0808-857 | s2cid = 205429626 }} It is demonstrated that with a lack of Pikachurin, there is an improper apposition of the bipolar cell dendritic tips to the photoreceptor ribbon synapses, resulting in alterations in synaptic signal transmission and visual function. The function of Pikachurin remains unknown, but it is a fact that pikachurin is critically involved in the normal photoreceptor ribbon synapse formation and also in physiological functions of visual perception.{{cite journal | vauthors = Hu H, Li J, Zhang Z, Yu M | title = Pikachurin interaction with dystroglycan is diminished by defective O-mannosyl glycosylation in congenital muscular dystrophy models and rescued by LARGE overexpression | journal = Neuroscience Letters | volume = 489 | issue = 1 | pages = 10–5 | date = February 2011 | pmid = 21129441 | pmc = 3018538 | doi = 10.1016/j.neulet.2010.11.056 }}

Congenital muscular dystrophies (CMD) such as muscle-eye-brain disease are caused by defective glycosylation of α-dystroglycan (α-DG) exhibit defective photoreceptor synaptic function. Pikachurin plays an essential role in CMD. Precise interactions between the photoreceptor ribbon synapse and the bipolar dendrites which are realized due to Pikachurin may advance our understanding of the molecular mechanisms underlying the retinal electrophysiological abnormalities observed in muscular dystrophy patients. The muscle-eye-brain dystrophy is caused by mutations in POMGnT1 or LARGE. These two genes mediated a post-translational modification on O-mannose, which is essential for pikachurin binding to dystroglycan, so people who suffer muscle-eye-disease have an hypoglycosylation of pikachurin-α-dystroglycan interactions.

Since pikachurin seems to provide better visual acuity, Sato et al. of the Osaka Bioscience Institute believe that the protein could be used to develop a treatment for retinitis pigmentosa and other eye disorders.{{cite news | url =http://www.yomiuri.co.jp/dy/features/science/20080722TDY02306.htm|title=Researchers: 'Pikachurin' protein linked with kinetic vision|publisher=Yomiuri Shimbun|date=2008-07-22|access-date= 2008-07-22 |archive-url = https://web.archive.org/web/20080727140433/http://www.yomiuri.co.jp/dy/features/science/20080722TDY02306.htm |archive-date = 2008-07-27}}

• Fibronectin type III domain
• Laminin G-like domain
• Sonic hedgehog, another protein named after a popular video game character.
• Zbtb7, an oncogene that was originally named "Pokemon".
• Aerodactylus, a genus of pre-historic pterosaurs named after Aerodactyl, a pterosaur in the Pokémon franchise.
• Binburrum, a family of beetles of which three members were scientifically named after the Pokémon Articuno, Zapdos, and Moltres.
• Nocticola pheromosa, a cockroach named after Pheromosa.

{{reflist|33em}}

• [http://inventorspot.com/articles/lightningfast_vision_protein_named_after_pikachu_16170 Lightning-Fast Vision Protein Named After Pikachu] {{Webarchive|url=https://web.archive.org/web/20170711112534/http://inventorspot.com/articles/lightningfast_vision_protein_named_after_pikachu_16170 |date=2017-07-11 }} - July 24, 2008

Category:Extracellular matrix proteins

Category:Genes on human chromosome 5