Loss of optineurin in vivo results in elevated cell death and alters axonal trafficking dynamics. PLoS One 2014;9(10):e109922
Date
10/21/2014Pubmed ID
25329564Pubmed Central ID
PMC4199637DOI
10.1371/journal.pone.0109922Scopus ID
2-s2.0-84908045074 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Mutations in Optineurin have been associated with ALS, glaucoma, and Paget's disease of bone in humans, but little is known about how these mutations contribute to disease. Most of the cellular consequences of Optineurin loss have come from in vitro studies, and it remains unclear whether these same defects would be seen in vivo. To answer this question, we assessed the cellular consequences of Optineurin loss in zebrafish embryos to determine if they showed the same defects as have been described in the in vitro studies. We found that loss of Optineurin resulted in increased cell death, as well as subtle cell morphology, cell migration and vesicle trafficking defects. However, unlike experiments on cells in culture, we found no indication that the Golgi apparatus was disrupted or that NF-κB target genes were upregulated. Therefore, we conclude that in vivo loss of Optineurin shows some, but not all, of the defects seen in in vitro work.
Author List
Paulus JD, Link BAAuthor
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Apoptosis
Axons
Biological Transport
Cell Cycle Proteins
Cell Movement
Conserved Sequence
Embryo, Nonmammalian
Eye Proteins
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Humans
Membrane Transport Proteins
Mice
Molecular Sequence Data
Mutation
Neural Crest
Protein Structure, Tertiary
Transcription Factor TFIIIA
Zebrafish