Nuclear carrier and RNA-binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changes.

Abstract

AIMS:

We aimed to investigate the role of the nuclear carrier and binding proteins, transportin 1 (TRN1) and transportin 2 (TRN2), TATA-binding protein-associated factor 15 (TAF15) and Ewing's sarcoma protein (EWS) in inclusion body formation in cases of frontotemporal lobar degeneration (FTLD) associated with fused in sarcoma protein (FTLD-FUS).

METHODS:

Eight cases of FTLD-FUS (five cases of atypical FTLD-U, two of neuronal intermediate filament inclusion body disease and one of basophilic inclusion body disease) were immunostained for FUS, TRN1, TRN2, TAF15 and EWS. Ten cases of FTLD associated with TDP-43 inclusions served as reference cases.

RESULTS:

The inclusion bodies in FTLD-FUS contained TRN1 and TAF15 and, to a lesser extent, EWS, but not TRN2. The patterns of immunostaining for TRN1 and TAF15 were very similar to that of FUS. None of these proteins was associated with tau or TDP-43 aggregations in FTLD.

CONCLUSIONS:

Data suggest that FUS, TRN1 and TAF15 may participate in a functional pathway in an interdependent way, and imply that the function of TDP-43 may not necessarily be in parallel with, or complementary to, that of FUS, despite each protein sharing many similar structural elements.

• Authors: Y S Davidson, A C Robinson, Q Hu, M Mishra, A Baborie, E Jaros, R H Perry, N J Cairns, A Richardson, A Gerhard, D Neary, J S Snowden, E H Bigio, D M A Mann
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 39 Issue 2 Pg. 157-65 (Feb 2013) ISSN: 1365-2990 [Electronic] England
• PMID: 22497712 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.

Chemical References

• DNA-Binding Proteins
• FUS protein, human
• RNA-Binding Protein EWS
• RNA-Binding Protein FUS
• TAF15 protein, human
• TATA-Binding Protein Associated Factors
• TNPO1 protein, human
• TNPO2 protein, human
• beta Karyopherins

Topics

• Adult
• DNA-Binding Proteins (metabolism)
• Female
• Frontotemporal Lobar Degeneration (metabolism)
• Humans
• Inclusion Bodies (metabolism)
• Male
• Middle Aged
• RNA-Binding Protein EWS (metabolism)
• RNA-Binding Protein FUS (metabolism)
• TATA-Binding Protein Associated Factors (metabolism)
• beta Karyopherins (metabolism)