CAPN5

Calpains are a 15-member class of calcium-activated nonlysosomal neutral proteases. They are involved in many cellular processes and are highly upregulated in pathological conditions. Some are ubiquitously expressed (CAPN1, CAPN2, CAPN4, CAPN5, CAPN7, and CAPN10), but others are thought to be localized in specific tissues. The monitoring of in vivo calpain activity is required for physiological, pathological, and therapeutic evaluations. This past decade, a tool for monitoring calpain activity in such conditions was developed using Forster resonance energy transfer (FRET)...

PURPOSE: To characterize the changes found in the electroretinography (ERG) recordings of patients with autosomal dominant neovascular inflammatory vitreoretinopathy and correlate with clinical stages of the disease. METHODS: Retrospective chart review. Bright- and dim-flash full-field scotopic, photopic, and 30-Hz flicker ERGs were obtained according to international standards. The scotopic ERGs were further processed to analyze the oscillatory potential. The patient described in the case report underwent full ERG testing; five patients composed the archival case series data and included scotopic ERG recordings...

Purpose: Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a devastating inherited autoimmune disease of the eye that displays features commonly seen in other eye diseases, such as retinitis pigmentosa and diabetic retinopathy. ADNIV is caused by a gain-of-function mutation in Calpain-5 (CAPN5), a calcium-dependent cysteine protease. Very little is known about the normal function of CAPN5 in the adult retina, and there are conflicting results regarding its role during mammalian embryonic development...

Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry...

Purpose: To identify the causative gene and investigate the corresponding mechanisms for an autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) family. Methods: Clinical examination and genetic analysis were performed in a Chinese ADNIV family. To dissect the molecular consequence, we used gene targeting to knock-in a patient's specific mutation in the mouse genome. Immunostaining and immunoprecipitation were harnessed to analyze the colocalization and interaction of CAPN5 with SLIT2 in photoreceptors...

Mutations that activate the protease calpain-5 ( CAPN5) cause a nonsyndromic adult-onset autoinflammatory eye disease characterized by uveitis, altered synaptic signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We describe a pediatric patient with severe inflammatory vitreoretinopathy accompanied by hearing loss and developmental delay associated with a novel, de novo CAPN5 missense mutation (c.865C>T, p.Arg289Trp) that shows greater hyperactivation of the calpain protease, indicating a genotype-phenotype correlation that links mutation severity to proteolytic activity and the possibility of earlier onset syndromic disease with auditory and neurological abnormalities...

CAPN5 has been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). Activation of CAPN5 may increase proteolysis and degradation of a wide range of substrates to induce degeneration in the retina and the nerve system. Thus, we developed an inhibitory intracellular single chain variable fragment (scFv) against CAPN5 as a potential way to rescue degeneration in ADNIV disease or in neuronal degeneration. We report that overexpression CAPN5 increases the levels of the auto-inflammatory factors toll like receptor 4 (TLR4), interleukin 1 alpha (IL1alpha), tumor necrosis factor alpha (TNFalpha) and activated caspase 3 in 661W photoreceptor-like cells and SHSY5Y neuronal-like cells...

OBJECTIVE: Our objective was to characterize CAPN5 gene expression in the mouse central nervous system. Mouse brain and eye sections were probed with two high-affinity RNA oligonucleotide analogs designed to bind CAPN5 RNA and one scramble, control oligonucleotide. Images were captured in brightfield. RESULTS: CAPN5 RNA probes were validated on mouse breast cancer tumor tissue. In the eye, CAPN5 was expressed in the ganglion cell, inner nuclear and outer nuclear layers of the retina...

PURPOSE: We report two new CAPN5 mutations associated with a phenotype of Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy. METHODS: We performed next generation sequencing in two patients with ADNIV phenotype; the variants identified were explored further. RESULTS: Patient 1 was heterozygous for CAPN5 c.799G>A, p.(Gly267Ser). Patient 2 was heterozygous for CAPN5 c.1126G>A, p.(Gly376Ser). Both amino acids are highly conserved across species...

OBJECTIVE: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. PATIENTS AND METHODS: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes...

PURPOSE: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments. METHODS: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions...

A total of nine non-coding variants on 11q13.5 predispose men to prostate cancer (PrCa). rs200331695 within the EMSY intron is associated with aggressive PrCa and two high linkage disequilibrium (LD) groups of single-nucleotide polymorphisms (SNPs) in the intergenic region are associated with PrCa death. Here, the cis-effect of the SNPs on gene expression using expression quantitative trait loci analysis was investigated. The regulatory potential was screened in prostate tumors (n = 41) and in whole blood (n = 99)...

PURPOSE OF REVIEW: Ophthalmologists and rheumatologists frequently have a miscommunication among themselves, and as a result differ in their opinion for patients consulting them with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent studies on this diagnosis. RECENT FINDINGS: The genetic basis of some rare forms of retinal vascular disease has recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; Behçet's disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; retinal imaging, including fluorescein angiography and other newer imaging modalities, has proven crucial to the identification and characterization of retinal vasculitis and its complications; although monoclonal antibodies to interleukin-17A or interleukin-1 beta failed in trials for Behçet's disease, antibodies to TNF-alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease...

The study is aimed at identifying selection footprints within the genome of Limousin cattle. With the use of Extended Haplotype Homozygosity test, supplemented with correction for variation in recombination rates across the genome, we created map of selection footprints and detected 173 significant (p < 0.01) core haplotypes being potentially under positive selection. Within these regions, a number of candidate genes associated inter alia with skeletal muscle growth (GDF15, BMP7, BMP4 and TGFB3) or postmortem proteolysis and meat maturation (CAPN1 and CAPN5) were annotated...

BACKGROUND: Despite some advances in recent years, the genetic control of gonadal sex differentiation during embryogenesis is still not completely understood. To identify new candidate genes involved in ovary and testis development, RNA-seq was used to define the transcriptome of embryonic chicken gonads at the onset of sexual differentiation (day 6.0/stage 29). RESULTS: RNA-seq revealed more than 1000 genes that were transcribed in a sex-biased manner at this early stage of gonadal differentiation...

A single amino acid mutation near the active site of the CAPN5 protease was linked to the inherited blinding disorder, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM #193235). In homology modeling with other calpains, this R243L CAPN5 mutation was situated in a mobile loop that gates substrate access to the calcium-regulated active site. In in vitro activity assays, the mutation increased calpain protease activity and made it far more active at low concentrations of calcium. To test whether the disease allele could yield an animal model of ADNIV, we created transgenic mice expressing human (h) CAPN5(R243L) only in the retina...

CAPN5 mutations have been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a blinding autoimmune eye disease. Here, we link a new CAPN5 mutation to ADNIV and model the three-dimensional structure of the resulting mutant protein. In our study, a kindred with inflammatory vitreoretinopathy was evaluated by clinical eye examinations, DNA sequencing, and protein structural modeling to investigate the disease-causing mutation. Two daughters of an affected mother demonstrated symptoms of stage III ADNIV, with posterior uveitis, cystoid macular edema, intraocular fibrosis, retinal neovascularization, retinal degeneration, and cataract...

BACKGROUND: The purpose of this project was to identify short hairpin RNA (shRNA) sequences that can suppress expression of human CAPN5 in which gain-of-function mutants cause autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). We created HEK293T cells that stably express an ADNIV disease allele, CAPN5-p.R243L. Transfection protocols were optimized for neuroblastoma SHSY5Y cells. The gene silencing effect of four different shRNA plasmids that target CAPN5 was tested...

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF hand motif characteristic of classical calpains but retains catalytic and Ca(2+) binding domains, and it contains a unique C-terminal domain. TRA-3, an ortholog of CAPN5, has been shown to be involved in necrotic cell death in Caenorhabditis elegans. CAPN5 is expressed throughout the CNS, but its expression relative to other calpains and subcellular distribution has not been investigated previously. Based on relative mRNA levels, Capn5 is the second most highly expressed calpain in the rat CNS, with Capn2 mRNA being the most abundant...

Exome sequencing indicated that the gene encoding the calpain-5 protease, CAPN5, is the likely cause of retinal degeneration and autoimmune uveitis in human patients with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM #193235). To explore the mechanism of ADNIV, a human CAPN5 disease allele was expressed in mouse retinas with a lentiviral vector created to express either the wild-type human (h) CAPN5 or the ADNIV mutant hCAPN5-R243L allele under a rhodopsin promoter with tandem green fluorescent protein (GFP) expression...