Pikachurin. besides known as agrin-like protein ( AGRINL ) and EGF-like. fibronectin type-III and laminin G-like domain-containing protein ( EGFLAM ) . is a hempen protein that in worlds is encoded by the EGFLAM cistron. Pikachurin is a dystroglycan-interacting protein which has an indispensable function in the precise interactions between the photoreceptor thread synapse and the bipolar dendrites. The binding with dystroglycan ( DG ) depends on several factors ( glycosylation of DG. presence of bivalent cations. presence of other proteins ) . A non-correct binding between pikachurin and DG is associated with muscular dystrophies that frequently involve oculus abnormalcies. Discovery and terminology
Pikachurin is an extracellular matrix-like retinal protein foremost described in 2008 in Japan by Shigeru Sato et Al. . and named after Pikachu. a character of the Pokemon franchise. The name of this “nimble” protein was inspired due to Pikachu’s “lightning-fast moves and flooring electric effects” . Pikachurin was ab initio identified in a microarray analysis of cistron look profiles of the retinas of wild-type and Otx2 smasher mice. A RT-PCR analysis was used to corroborate that Otx2 regulates the look of pikachurin. it was known because there was an absence of look of pikachurin in the Otx2 mice retina. so it indicates that Otx2 regulates pikachurin. The localisation of pikachurin to synaptic cleft in the photoreceptor thread synapse was determined utilizing fluorescent antibodies. Tissue aiming of cistron break of pikachurin was used to find that this protein is necessary for proper synaptic signal transmittal and ocular map. ?-dystroglycan was shown to interact with pikachurin through immunoprecipitation. Pikachurin-dystroglycan interaction
Dystroglycan ligand with other proteins is indispensable. Glycosylation of dystroglycan is necessary for its ligand binding activity. Mutants in glycosyltransferase enzymes cause unnatural glycosylation of dystroglycan. This hipoglycosylation it’s associated with less adhering with other proteins and causes some inborn muscular dystrophy. Pikachurin is the most late identified dystroglycan ligand protein and is localized in the synaptic cleft in the photoreceptor thread synapse. The binding between dystroglycan and pikachurin requires bivalent cations. Ca2+ produces strongest binding ; Mn2+ produces merely weak bindings and no binding with Mg2+ entirely. Dystroglycan has different spheres that allow multiple Ca2+ sites to organize a stable pikachurin-dystroglycan connexion.
This shows that pikachurin can organize oligomeric constructions ; and suggests the possibility of constellating effects can be of import 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 consequence with pikachurin-DG ligand. This shows that are differences between the binding of pikachurin-DG binding and DG binding with other proteins. Pikachurin seems to hold more spheres to adhere with DG than other proteins. For illustration. experiments in ligand competition shows that presence of pikachurin inhibits laminin-111 adhering with DG. but high concentrations of laminin-111 do non suppress pikachurin binding to DG.
FunctionThe protein is colocalized with both dystrophin and dystroglycan at the thread synapses. Pikachurin. along with laminin. perlecan. agrin. neurexin. binds to ?-dystroglycan in the extracellular infinite. As such. pikachurin. every bit good as the other previously-mentioned proteins. is necessary for the proper operation of dystroglycan. Pikachurin is necessary for the apposition of presynaptic and postsynaptic end point in the thread synapse ; omission of pikachurin causes an unnatural electroretinogram. likewise to the omission of nestin.
Ribbon synapse relation
Ribbon synapse
Synapse formation is important for the mammalian CNS ( cardinal nervous system ) to work right. Retinal photoreceptors finish at the axon terminus which forms a specialised construction. the thread synapse. which specifically connects photoreceptor synaptic terminuss with bipolar and horizontal cell terminuss in the outer plexiform bed ( OPL ) of the retina. It is clear that Pikachurin. an extracellular matrix–like retinal protein. is localized to the synaptic cleft in the photoreceptor thread synapse. It is demonstrate that with a deficiency of Pikachurin. there is an improper apposition of the bipolar cell dendritic tips to the photoreceptor thread synapses. ensuing in changes in synaptic signal transmittal and ocular map. The map of Pikachurin remains unknown. but it is a fact that pikachurin is critically involved in the normal photoreceptor thread synapse formation and besides in physiological maps of ocular perceptual experience. It is indispensable for both eye-to-brain transmittal of ocular signals and the manner the oculus paths traveling. or kinetic. objects in the field of vision. Without Pikachurin. it can take up to three times longer for ocular signals to be sent to the brain’s vision centre. Associated pathologies: muscular dystrophies
Congenital muscular dystrophies ( CMD ) such as muscle-eye-brain disease are caused by faulty glycosylation of ?-dystroglycan ( ?-DG ) exhibit faulty photoreceptor synaptic map. Pikachurin plays an indispensable regulation in CMD. Precise interactions between the photoreceptor thread synapse and the bipolar dendrites which are realized due to Pikachurin may progress our apprehension of the molecular mechanisms underlying the retinal electrophysiological abnormalcies observed in muscular dystrophy patients. The muscle-eye-brain dystrophy is caused by mutants in POMGnT1 or LARGE. These two cistrons mediated a post-translational alteration on O-mannose. which is indispensable for pikachurin binding to dystroglycan. so people who suffer muscle-eye-disease have an hypoglycosylation of pikachurin-?-dystroglycan interactions. Curative applications
Since pikachurin seems to supply better ocular sharp-sightedness. Sato et Al. of the Osaka Bioscience Institute believe that the protein could be used to develop a intervention for retinitis pigmentosa and other oculus upsets.
