The receptor for activated C-kinase 1 (RACK1) is a conserved structural protein of 40S ribosomes. Strikingly, deletion of RACK1 in yeast homolog Asc1 is not lethal. Mammalian RACK1 also interacts with many nonribosomal proteins, hinting at several extraribosomal functions. A knockout mouse for RACK1 has not previously been described. We produced the first RACK1 mutant mouse, in which both alleles of RACK1 gene are defective in RACK1 expression (ΔF/ΔF), in a pure C57 Black/6 background. In a sample of 287 pups, we observed no ΔF/ΔF mice (72 expected). Dissection and genotyping of embryos at various stages showed that lethality occurs at gastrulation. Heterozygotes (ΔF/+) have skin pigmentation defects with a white belly spot and hypopigmented tail and paws. ΔF/+ have a transient growth deficit (shown by measuring pup size at P11). The pigmentation deficit is partly reverted by p53 deletion, whereas the lethality is not. ΔF/+ livers have mild accumulation of inactive 80S ribosomal subunits by polysomal profile analysis. In ΔF/+ fibroblasts, protein synthesis response to extracellular and pharmacological stimuli is reduced. These results highlight the role of RACK1 as a ribosomal protein converging signaling to the translational apparatus. © 2012 Springer Basel.
|Titolo:||RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency|
|Parole Chiave:||40S; Asc1p; eIF6; Initiation; PKC beta; Animals; Cells, Cultured; Embryo Loss; Embryo, Mammalian; Gene Knockout Techniques; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuropeptides; Phenotype; RNA Interference; RNA, Small Interfering; Tumor Suppressor Protein p53; Pigmentation; Protein Biosynthesis; Cell Biology; Molecular Biology; Molecular Medicine; Pharmacology; Cellular and Molecular Neuroscience|
|Settore Scientifico Disciplinare:||Settore BIO/06 - Anatomia Comparata e Citologia|
|Data di pubblicazione:||apr-2013|
|Digital Object Identifier (DOI):||10.1007/s00018-012-1215-y|
|Appare nelle tipologie:||01 - Articolo su periodico|