The Journal of biological chemistry, 2011-01, Vol.286 (1), p.726-736
2011
Details
- Autor(en) / Beteiligte
- Titel
- Prefoldin 5 Is Required for Normal Sensory and Neuronal Development in a Murine Model
- Ist Teil von
- The Journal of biological chemistry, 2011-01, Vol.286 (1), p.726-736
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Molecular chaperones and co-chaperones are crucial for cellular development and maintenance as they assist in protein folding and stabilization of unfolded or misfolded proteins. Prefoldin (PFDN), a ubiquitously expressed heterohexameric co-chaperone, is necessary for proper folding of nascent proteins, in particular, tubulin and actin. Here we show that a genetic disruption in the murine Pfdn5 gene, a subunit of prefoldin, causes a syndrome characterized by photoreceptor degeneration, central nervous system abnormalities, and male infertility. Our data indicate that a missense mutation in Pfdn5, may cause these phenotypes through a reduction in formation of microtubules and microfilaments, which are necessary for the development of cilia and cytoskeletal structures, respectively. The diversity of phenotypes demonstrated by models carrying mutations in different PFDN subunits suggests that each PFDN subunit must confer a distinct substrate specificity to the prefoldin holocomplex.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M110.177352Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3013031
- Format
- –
- Schlagworte
- Actin, Actin Cytoskeleton - genetics, Actin Cytoskeleton - metabolism, Animal models, Animals, Base Sequence, Cell Proliferation, Cell Survival - genetics, Central nervous system, Central Nervous System - abnormalities, Central Nervous System - metabolism, Chaperone Chaperonin, Chaperones, Cilia, Cytoskeleton, Data processing, Female, Gene Regulation, Humans, Hypogonadism - genetics, Infertility, Male, Mice, Microfilaments, Microtubules, Microtubules - genetics, Microtubules - metabolism, Missense mutation, Models, Animal, Models, Molecular, Molecular Chaperones - chemistry, Molecular Chaperones - genetics, Molecular Chaperones - metabolism, Mouse Genetics, Mutagenesis, Mutation, Missense - drug effects, Neurodevelopment, Nitrosourea Compounds - pharmacology, Photoreceptors, Point Mutation - drug effects, Protein Conformation, Protein Folding, retinal degeneration, Retinal Photoreceptor Cell Inner Segment - metabolism, Retinal Photoreceptor Cell Outer Segment - metabolism, Saccharomyces cerevisiae - cytology, Sensory Receptor Cells - cytology, Sensory Receptor Cells - metabolism, Substrate specificity, Tubulin