accumulation of endogenous litaf in aggresomes积累内生litaf aggresomes.pdfVIP

Accumulation of Endogenous LITAF in Aggresomes Heather E. Eaton¤a, Julie Metcalf¤b, Andressa Ferreira Lacerda, Craig R. Brunetti* Department of Biology, Trent University, Peterborough, Ontario, Canada Abstract LITAF is a 161 amino acid cellular protein which includes a proline rich N-terminus and a conserved C-terminal domain known as the simple-like domain. Mutations in LITAF have been identified in Charcot-Marie tooth disease, a disease characterized by protein aggregates. Cells transfected with cellular LITAF reveal that LITAF is localized to late endosomes/ lysosomes. Here we investigated the intracellular localization of endogenous LITAF. We demonstrated that endogenous LITAF accumulates at a discrete cytoplasmic site in BGMK cells that we identify as the aggresome. To determine the domain within LITAF that is responsible for the localization of LITAF to aggresomes, we created a construct that contained the C- terminal simple-like domain of LITAF and found that this construct also localizes to aggresomes. These data suggest the simple-like domain is responsible for targeting endogenous LITAF to the aggresome. Citation: Eaton HE, Metcalf J, Lacerda AF, Brunetti CR (2012) Accumulation of Endogenous LITAF in Aggresomes. PLoS ONE 7(1): e30003. doi:10.1371/ journal.pone.0030003 Editor: Vladimir N. Uversky, University of South Florida College of Medicine, United States of America Received June 9, 2011; Accepted December 8, 2011; Published January 19, 2012 Copyright: 2012 Eaton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded through a Natural Sciences and Engineering Research