PICK1

The human memory-associated protein KIBRA regulates synaptic plasticity and trafficking of AMPA-type glutamate receptors, and is implicated in multiple neuropsychiatric and cognitive disorders. How KIBRA forms complexes with and regulates AMPA receptors remains unclear. Here, we show that KIBRA does not interact directly with the AMPA receptor subunit GluA2, but that PICK1, a key regulator of AMPA receptor trafficking, can serve as a bridge between KIBRA and GluA2. We identified structural determinants of KIBRA-PICK1-AMPAR complexes by investigating interactions and cellular expression patterns of different combinations of KIBRA and PICK1 domain mutants...

INTRODUCTION: The development of reproducible tools for the rapid genotyping of thousands of genetic markers (SNPs) has promoted cross border collaboration in the study of sheep genetic diversity on a global scale. METHODS: In this study, we collected a comprehensive dataset of 239 African and Eurasian sheep breeds genotyped at 37,638 filtered SNP markers, with the aim of understanding the genetic structure of 22 North African (NA) sheep breeds within a global context...

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N -methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 ( DLG4 ) and protein interacting with C kinase 1 ( PICK1 ) reached genome-wide significance ( P < 5 × 10 - 8 ) for BF% and/or BMI...

BACKGROUND: Infertility affects approximately 10-15% of reproductive-age men worldwide, and genetic causes play a role in one-third of cases. As a Bin-Amphiphysin-Rvs (BAR) domain protein, protein interacting with C-kinase 1 (PICK1) deficiency could lead to impairment of acrosome maturation. However, its effects on auxiliary germ cells such as Sertoli cells are unknown. PURPOSE: The present work was aimed to use multi-omics analysis to research the effects of PICK1 deficiency on Sertoli cells and to identify effective biomarkers to distinguish fertile males from infertile males caused by PICK1 deficiency...

The α-amino-3-hydroxy-5-methylisoxazole-4-isoxazolepropionic acid receptor (AMPAR) has been recognized to play a vital role in the development of neuropathic pain. Recent studies have indicated that protein kinase C (PKC) and protein interacting with C-kinase 1 (PICK1) are involved in the phosphorylation of AMPARs. However, whether PKC and PICK1 were involved in the AMPAR phosphorylation in the trigeminal ganglion (TG) to participate in orofacial neuropathic pain remains enigmatic. A behavioral test was utilized to evaluate the head withdrawal threshold (HWT) after chronic constriction injury of the infraorbital nerve (CCI-ION)...

Protein disulfide isomerase (PDI) is a redox-active enzyme and also serves as a nitric oxide donor causing S-nitrosylation of cysteine residues in various proteins. Although PDI knockdown reduces α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR)-mediated neuronal activity, the underlying mechanisms are largely unknown. In the present study, we found that under physiological condition PDI knockdown increased CaMKII activity (phosphorylation) in the mouse hippocampus. However, PDI siRNA inhibited protein phosphatase (PP) 2A-mediated GluA2 S880 dephosphorylation by increasing PP2A oxidation, independent of S-nitrosylation...

Protein interacting with C kinase 1 (PICK1) is an AMPA receptor binding protein that works in conjunction with glutamate receptor interacting protein (GRIP) to balance the number of GluA2-containing AMPARs in the synapse. In male mice, disrupting PICK1 in the medial prefrontal cortex (mPFC) leads to a decrease in cue-induced cocaine seeking and disrupting GRIP in the mPFC has the opposing effect, consistent with other evidence that removal of GluA2-containing AMPARs potentiates reinstatement. However, PICK1 does not seem to play the same role in female mice, as knockdown of either PICK1 or GRIP in the mPFC leads to similar increases in cue-induced cocaine seeking...

Acute liver injury (ALI) may manifest at any phase of sepsis, yet an explicit therapeutic approach remains elusive. In this study, LPS and cecum ligation and puncture (CLP) were utilized to establish an inflammatory cell model and a murine model of sepsis-induced liver injury, respectively, aiming to explore the potential protective effect of protein interacting with C α kinase 1 (PICK1) on sepsis-induced ALI and its underlying mechanisms. In both the cell supernatant and the murine whole blood, the concentrations of inflammatory factors were quantified by ELISA, while the protein and mRNA expressions of PICK1, cleaved-PARP-1, caspase1, TLR4, IκBα, and NF-κB were assessed via western blot and qRT-PCR...

Iron accumulation, which is controlled by transferrin receptor 1 (TfR1), modulates hypoxia-inducible factor-1α (HIF-1α) activation and angiogenesis of hypoxic endothelial cells. The study examined the role of protein interacting with C-kinase 1 (PICK1), a scaffold protein containing PDZ domain, in regulating glycolysis and angiogenesis of hypoxic vascular endothelial cells through its potential effect on TfR1, which features a supersecondary structure that interacts with the PDZ domain. Iron chelator deferoxamine and TfR1 siRNA were employed to assess the impact of iron accumulation on angiogenesis, while the effects of PICK1 siRNA and overexpressing lentivirus on TfR1-mediated iron accumulation were also investigated in hypoxic human umbilical vein vascular endothelial cells (HUVECs)...

Long-term potentiation (LTP) is one of the major cellular mechanisms for learning and memory. Activity-dependent increases in surface AMPA receptors (AMPARs) are important for enhanced synaptic efficacy during LTP. Here, we report a novel function of a secretory trafficking protein, ICA69, in AMPAR trafficking, synaptic plasticity, and animal cognition. ICA69 is first identified as a diabetes-associated protein well characterized for its function in the biogenesis of secretory vesicles and trafficking of insulin from ER, Golgi to post-Golgi in pancreatic beta cells...

INTRODUCTION: Bin/Amphiphysin/Rvs167 (BAR) domain superfamily proteins are considered to be able to induce membrane curvature. PICK1 is a unique protein consisting of both a PDZ and a BAR domain that has been associated with many diseases. PICK1 can force membrane curvature during receptor-mediated endocytosis. In addition to understanding how the N-BAR domain can force membrane curvature, it is also of particular interest to understand the hidden connections between structural and mechanical properties of the PICK1 BAR dimers...

Group I metabotropic glutamate receptors (mGluRs) play important roles in many neuronal processes and are believed to be involved in synaptic plasticity underlying the encoding of experience, including classic paradigms of learning and memory. These receptors have also been implicated in various neurodevelopmental disorders, such as Fragile X syndrome and autism. Internalization and recycling of these receptors in the neuron are important mechanisms to regulate the activity of the receptor and control the precise spatiotemporal localization of these receptors...

CONTEXT: Metabolic disorders such as obesity represent a major health challenge. Obesity alone has reached epidemic proportions, with at least 2.8 million people worldwide dying annually from diseases caused by overweight or obesity. The brain-metabolic axis is central to maintain homeostasis under metabolic stress via an intricate signaling network of hormones. Protein interacting with C kinase 1 (PICK1) is important for the biogenesis of various secretory vesicles, and we have previously shown that PICK1-deficient mice have impaired secretion of insulin and growth hormone...

OBJECTIVE: The protein interacting with C kinase 1 (PICK1) plays a critical role in vesicle trafficking, and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome, which eventually disrupts acrosome formation and leads to male infertility. METHODS: An azoospermia sample was filtered, and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient. We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene, c...

AIMS: Hypoxia is an important feature of nasopharyngeal carcinoma (NPC). "Protein interacting with PRKCA 1" (PICK1) is commonly downregulated in human malignancies and is functionally related to poor prognosis. However, there is a limited understanding of the upstream mechanisms regulating PICK1 currently. MAIN METHODS: PICK1 and HIF-1α expression levels were analyzed by Immunohistochemistry (IHC), western blotting, and quantitative real-time PCR assay. Protein stability and ubiquitin assays were used to investigate PICK1 protein degradation...

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria ( KIT , ADAMTS13 , GBA1 , and PIG-A genes, respectively). In Castleman disease, improper ETS1 , PTPN6 , TGFBR2 , DNMT3A , and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF , MAP2K1 , MAP3K1 , ARAF , ERBB3 , NRAS , KRAS , PICK1 , PIK3R2 , and PIK3CA ...

AIMS: To explore the underlying mechanism by which low-frequency KRAS mutations result in extensive EndMT occurrence. METHODS: Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRASG12D , KRASWT , or KRASNC lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR-3131 and detection of its downstream target, and miR-3131 inhibitor in reversing the EndMT process induced by KRASG12D -transfected HUVECs and bAVM endothelial cells (ECs) were explored...

Muscarinic acetylcholine receptors (mAChRs) have been shown to play significant roles in the regulation of normal cognitive processes in the hippocampus, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are also involved in these processes. This study aims to explore the mAChR-mediated regulation of AMPARs GluA2 trafficking and to reveal the key proteins and the signaling cascade involved in this process. Primary hippocampal neurons, as cell models, were treated with agonist 77-LH-28-1 and antagonist VU0255035, Fsc231, and APV...

BACKGROUND: Recent studies indicate that cell mechanics are associated with malignancy through its impact on cell migration and adhesion. Gliomas are the most common primary malignant brain tumors. Low-grade gliomas (LGGs) include diffuse LGGs (WHO grade II) and intermediate-grade gliomas (WHO grade III). Few studies have focused on membrane tension in LGGs. Herein, we assessed the prognostic value of plasma membrane tension-related genes (MTRGs) in LGGs. METHODS: We selected plasma MTRGs identified in previous studies for analysis...

[This corrects the article DOI: 10.1155/2021/9884297.].