Title: Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1α) docking protein
Authors: Ferrar, Tony *
Chamousset, Delphine *
De Wever, Veerle
Nimick, Mhairi
Andersen, Jens
Trinkle-Mulcahy, Laura
Moorhead, Greg B G # ×
Issue Date: Feb-2012
Series Title: Biology open vol:1 issue:2 pages:128-39
Article number: 10.1242/bio.2011049
Abstract: The promiscuous activity of protein phosphatase one (PP1) is controlled in the cell by associated proteins termed regulatory or targeting subunits. Using biochemical and proteomic approaches we demonstrate that the autosomal recessive nonsyndromic hearing loss gene, taperin (C9orf75), encodes a protein that preferentially docks the alpha isoform of PP1. Taperin associates with PP1 through a classic 'RVxF' motif and suppresses the general phosphatase activity of the enzyme. The steady-state localization of taperin is predominantly nuclear, however we demonstrate here that the protein can shuttle between the nucleus and cytoplasm and that it is found complexed to PP1 in both of these cellular compartments. Although originally identified as a hearing loss gene, Western blot analyses with taperin-specific antibodies revealed that the protein is widely expressed across mammalian tissues as multiple splice variants. Taperin is a recent proteome addition appearing during the vertebrate lineage with the PP1 binding site embedded within the most conserved region of the protein. Taperin also shares an ancestral relationship with the cytosolic actin binding protein phostensin, another PP1 interacting partner. Quantitative Stable Isotope Labeling by Amino acids in Culture (SILAC)-based mass spectrometry was employed to uncover additional taperin binding partners, and revealed an interaction with the DNA damage response proteins Ku70, Ku80, PARP and topoisomerases I and IIα. Consistent with this, we demonstrate the active recruitment of taperin to sites of DNA damage. This makes taperin a new addition to the family of PP1 targeting subunits involved in the DNA damage repair pathway.
ISSN: 2046-6390
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
* (joint) first author
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
Ferraretal_2011_TaperinPhostensin.pdf Published 3332KbAdobe PDFView/Open


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science