@article {663, title = {Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses.}, journal = {Invest Ophthalmol Vis Sci}, volume = {57}, year = {2016}, month = {2016 05 01}, pages = {2509-21}, abstract = {

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.

RESULTS: Most CAPN5 genetic variation occurs outside its protease core; and searches of cancer and epilepsy/autism genetic databases found no variants similar to hyperactivating retinal disease alleles. The mouse retina expressed one transcript for CAPN5 plus those of nine other calpains, similar to the human retina. In Y79 retinoblastoma cells, the level of CAPN5 transcript was very low. Immunohistochemistry detected CAPN5 expression in the inner and outer nuclear layers and at synapses in the outer plexiform layer. Western analysis of fractionated retinal extracts confirmed CAPN5 synapse localization. Western blots of fractionated brain neuronal extracts revealed distinct subcellular patterns and the potential presence of autoproteolytic CAPN5 domains.

CONCLUSIONS: CAPN5 is moderately expressed in the retina and, despite higher expression in other tissues, hyperactive disease mutants of CAPN5 only manifest as eye disease. At the cellular level, CAPN5 is expressed in several different functional compartments. CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles.

}, keywords = {Animals, Blotting, Western, Calpain, Cattle, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Male, Mice, Neoplasms, Experimental, Photoreceptor Cells, Retina, Retinal Neoplasms, Retinoblastoma, RNA, Neoplasm, Synapses, Tumor Cells, Cultured}, issn = {1552-5783}, doi = {10.1167/iovs.15-18680}, author = {Schaefer, Kellie A and Toral, Marcus A and Velez, Gabriel and Cox, Allison J and Baker, Sheila A and Borcherding, Nicholas C and Colgan, Diana F and Bondada, Vimala and Mashburn, Charles B and Yu, Chen-Guang and Geddes, James W and Tsang, Stephen H and Bassuk, Alexander G and Mahajan, Vinit B} } @article {149, title = {Mutations in prickle orthologs cause seizures in flies, mice, and humans.}, journal = {American journal of human genetics}, volume = {88}, year = {2011}, month = {2011 Feb 11}, pages = {138-49}, abstract = {

Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.

}, keywords = {Animals, Blotting, Western, Brain, Calcium, Carrier Proteins, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Epilepsies, Myoclonic, Female, Heterozygote, Humans, Immunoenzyme Techniques, In Situ Hybridization, Male, Mice, Mice, Knockout, Mutation, Nerve Tissue Proteins, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Seizures, Tumor Suppressor Proteins, Zebrafish, Zebrafish Proteins}, author = {Tao, Hirotaka and Manak, J Robert and Sowers, Levi and Mei, Xue and Kiyonari, Hiroshi and Abe, Takaya and Dahdaleh, Nader S and Yang, Tian and Wu, Shu and Chen, Shan and Fox, Mark H and Gurnett, Christina and Montine, Thomas and Bird, Thomas and Shaffer, Lisa G and Rosenfeld, Jill A and McConnell, Juliann and Madan-Khetarpal, Suneeta and Berry-Kravis, Elizabeth and Griesbach, Hilary and Saneto, Russell P and Scott, Matthew P and Antic, Dragana and Reed, Jordan and Boland, Riley and Ehaideb, Salleh N and El-Shanti, Hatem and Mahajan, Vinit B and Ferguson, Polly J and Axelrod, Jeffrey D and Lehesjoki, Anna-Elina and Fritzsch, Bernd and Slusarski, Diane C and Wemmie, John and Ueno, Naoto and Bassuk, Alexander G} } @article {151, title = {Seroreactivity against aqueous-soluble and detergent-soluble retinal proteins in posterior uveitis.}, journal = {Archives of ophthalmology}, volume = {129}, year = {2011}, month = {2011 Apr}, pages = {415-20}, abstract = {

To characterize the seroreactivity against retinal proteins in patients with posterior uveitis, retinal disease of noninflammatory origin, and healthy controls.

}, keywords = {Adolescent, Adult, Autoantibodies, Autoantigens, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Eye Proteins, Female, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Retina, Retinal Degeneration, Solubility, Uveitis, Posterior, Young Adult}, author = {Ko, Audrey C and Brinton, Jason P and Mahajan, Vinit B and Zimmerman, Bridget and Brinton, Gregory S and Stone, Edwin M and Folk, James C and Mullins, Robert F} }