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GRIK4 Membrane Protein Introduction

Introduction of GRIK4

Glutamate receptor ionotropic, kainate 4 (GRIK4) is a subunit of the kainate receptors (KARs). Totally, KARs assemble as tetramers from five subunits, GRIK1-5. GRIK1-3 subunits have low-affinity agonist binding sites, while GRIK4 and GRIK5 have high-affinity sites. Unlike other KARs, which are widely distributed in the central nervous system (CNS), GRIK4 subunits are expressed primarily within the cornu ammonis 3 (CA3) region of the hippocampus where it co-assembles pre-and post-synaptically with GRIK2. Due to their high and restricted expression in these tissues, GRIK4-knockout mice provide an interesting mouse model in which to evaluate the role of KARs in hippocampus-dependent behaviors.

Basic Information of GRIK4
Protein Name Glutamate receptor ionotropic, kainate 4
Gene Name GRIK4
Aliases EAA1, KA1
Organism Homo sapiens (Human)
UniProt ID Q16099
Transmembrane Times 3
Length (aa) 956
Sequence MPRVSAPLVLLPAWLVMVACSPHSLRIAAILDDPMECSRGERLSITLAKNRINRAPERLGKAKVEVDIFELLRDSEYETAETMCQILPKGVVAVLGPSSSPASSSIISNICGEKEVPHFKVAPEEFVKFQFQRFTTLNLHPSNTDISVAVAGILNFFNCTTACLICAKAECLLNLEKLLRQFLISKDTLSVRMLDDTRDPTPLLKEIRDDKTATIIIHANASMSHTILLKAAELGMVSAYYTYIFTNLEFSLQRMDSLVDDRVNILGFSIFNQSHAFFQEFAQSLNQSWQENCDHVPFTGPALSSALLFDAVYAVVTAVQELNRSQEIGVKPLSCGSAQIWQHGTSLMNYLRMVELEGLTGHIEFNSKGQRSNYALKILQFTRNGFRQIGQWHVAEGLSMDSHLYASNISDTLFNTTLVVTTILENPYLMLKGNHQEMEGNDRYEGFCVDMLKELAEILRFNYKIRLVGDGVYGVPEANGTWTGMVGELIARKADLAVAGLTITAEREKVIDFSKPFMTLGISILYRVHMGRKPGYFSFLDPFSPGVWLFMLLAYLAVSCVLFLVARLTPYEWYSPHPCAQGRCNLLVNQYSLGNSLWFPVGGFMQQGSTIAPRALSTRCVSGVWWAFTLIIISSYTANLAAFLTVQRMDVPIESVDDLADQTAIEYGTIHGGSSMTFFQNSRYQTYQRMWNYMYSKQPSVFVKSTEEGIARVLNSNYAFLLESTMNEYYRQRNCNLTQIGGLLDTKGYGIGMPVGSVFRDEFDLAILQLQENNRLEILKRKWWEGGKCPKEEDHRAKGLGMENIGGIFVVLICGLIVAIFMAMLEFLWTLRHSEATEVSVCQEMVTELRSIILCQDSIHPRRRRAAVPPPRPPIPEERRPRGTATLSNGKLCGAGEPDQLAQRLAQEAALVARGCTHIRVCPECRRFQGLRARPSPARSEESLEWEKTTNSSEPE

Functions of GRIK4 Membrane Protein

GRIK4 has been studied for its importance for the central nervous system. Gene variation in the GRIK4, the gene coding for GRIK4, results in behavioral symptomatology consistent with brain diseases such as autism as well as in alterations of synaptic function. Mice with a deletion of GRIK4 have reduced anxiety and an antidepressant-like phenotype. Moreover, these animals are hyperlocomotive and display impaired sensorimotor gating. The GRIK4 kainate receptor subunit is necessary for spatial learning and memory. In the context of kainate-induced excitotoxicity, GRIK4 ablation affects the activation of the c-Jun N-terminal kinase (JNK) pathway. In brief, GRIK4 may be relevant to the understanding and treatment of human neuropsychiatric and neurodegenerative disorders.

GRIK4 Membrane Protein Introduction Fig.1 Scheme of kainite receptor subunits. (Pinheiro, 2006)

Application of GRIK4 Membrane Protein in Literature

  1. Kristensen O., et al. The structure of a high-affinity kainate receptor: GluK4 ligand-binding domain crystallized with kainate. Structure. 2016, 24(9): 1582-1589. PubMed ID: 27524200

    This study reported the X-ray structure of GluK4 ligand binding domain with kainite at 2.05 Å resolution, together with thermofluor and radiolabel binding affinity data. These results may explain the high binding affinity of GluK4 for kainate.

  2. Catches J.S., et al. Genetic ablation of the GluK4 kainate receptor subunit causes anxiolytic and antidepressant-like behavior in mice. Behavioural Brain Research. 2012, 228(2): 406-414. PubMed ID: 22203159

    This study investigated the role of GluK4 subunit in mood disorders. Using GRIK4-deficient mice, the authors tested the behavior of mice with elevated zero-maze, marble-burying test, forced swim test, and the sucrose preference test. The results showed that GRIK-deficient mice had reduced anxiety and an antidepressant-like phenotype.

  3. Fernandes H.B., et al. High-affinity kainate receptor subunits are necessary for ionotropic but not metabotropic signaling. Neuron. 2009, 63(6): 818-829. PubMed ID: 19778510

    This study investigated the importance of high-affinity kainate receptor subunits: GluK4 and GluK5 for ionotropic signaling.

  4. Aller M.I., et al. Increased dosage of high-affinity kainate receptor gene GRIK4 alters synaptic transmission and reproduces autism spectrum disorders features. Journal of Neuroscience the Official Journal of the Society for Neuroscience. 2015, 35(40): 13619-28. PubMed ID: 26446216

    The de novo copy number variations of GRIK4, a gene coding for the GluK4 subunit of the kainate receptors, is implicated as a risk factor for mental retardation or autism. This study showed that mice overexpressing GRIK4 in the forebrain displayed social impairment, enhanced anxiety, and depressive states, altered synaptic transmission, etc.

  5. Lowry E.R., et al. The GluK4 kainate receptor subunit regulates memory, mood, and excitotoxic neurodegeneration. Neuroscience. 2013, 235(14): 215-225. PubMed ID: 23357115

    This study investigated the importance of GluK4 kainate receptor for the central nervous system, using GluK4-deficient mice. The results showed that this subunit played a critical role in memory, mood, and excitotoxic neurodegeneration.

GRIK4 Preparation Options

Considering the importance of GRIK4 for the central nervous system, the investigations of the molecular mechanisms and their therapeutic potential is expected to be valued in the future. To help researchers in their membrane protein studies, Creative Biolabs offers various strategies and approaches to isolate, stabilize, and/or crystalize your targets in the functional forms. From our various preparation options, you can always find a proper environment or format that adapts to your protein chemistry. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GRIK4 antibody development services.


Our mission is to provide our customers with the best-quality membrane targets for their brilliant studies and discovery projects. To learn more about our services please contact us directly or send us an inquiry.

Reference

  1. Pinheiro P and Mulle C. (2006). Kainate receptors. Cell and tissue research. 326(2): 457-482.

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