Accumulation of the PX domain mutant Frank-ter Haar syndrome protein Tks4 in aggresomes.

Adam, C. and Fekete, A. and Bogel, G. and Nemeth, Z. and Tokesi, N. and Pesti, Szabolcs and Ovádi, Judit and Liliom, Károly and Buday, László (2015) Accumulation of the PX domain mutant Frank-ter Haar syndrome protein Tks4 in aggresomes. CELL COMMUNICATION AND SIGNALING, 13 (1). p. 33. ISSN 1478-811X


Download (1MB) | Preview


BACKGROUND: Cells deploy quality control mechanisms to remove damaged or misfolded proteins. Recently, we have reported that a mutation (R43W) in the Frank-ter Haar syndrome protein Tks4 resulted in aberrant intracellular localization. RESULTS: Here we demonstrate that the accumulation of Tks4(R43W) depends on the intact microtubule network. Detergent-insoluble Tks4 mutant colocalizes with the centrosome and its aggregate is encaged by the intermediate filament protein vimentin. Both the microtubule inhibitor nocodazole and the histone deacetylase inhibitor Trichostatin A inhibit markedly the aggresome formation in cells expressing Tks4(R43W). Finally, pretreatment of cells with the proteasome inhibitor MG132 markedly increases the level of aggresomes formed by Tks4(R43W). Furthermore, two additional mutant Tks4 proteins (Tks4(1-48) or Tks4(1-341)) have been investigated. Whereas the shorter Tks4 mutant, Tks4(1-48), shows no expression at all, the longer Tks4 truncation mutant accumulates in the nuclei of the cells. CONCLUSIONS: Our results suggest that misfolded Frank-ter Haar syndrome protein Tks4(R43W) is transported via the microtubule system to the aggresomes. Lack of expression of Tks4(1-48) or aberrant intracellular expressions of Tks4(R43W) and Tks4(1-341) strongly suggest that these mutations result in dysfunctional proteins which are not capable of operating properly, leading to the development of FTHS.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 23 Jul 2015 13:37
Last Modified: 23 Jul 2015 13:37

Actions (login required)

Edit Item Edit Item