Journal of Amino Acids

Review Article

Drosophila Answers to TDP-43 Proteinopathies

Table 2

Ectopic expression of TDP-43 mutants.
Human TDP-43 mutations
 Q331KEye [7]
 M337VEye [7]
 M337VEye [12]
 M337VEye [15]
 A315TEye [13]
 G287SPan-neural, ubiquitary [8]
 A315TPan-neural, ubiquitary, eye [8]
 G348CPan-neural, ubiquitary [8]
 A382TPan-neural, ubiquitary [8]
 N390DPan-neural, ubiquitary [8]
Other mutants
 TDP-43 T202Eye[11]
 TDP-43 NES-mutEye [12]
 TDP-43 NLS-mutEye [12]
 TDP-43 ΔNLSEye, pan-neural, ubiquitary [8]
 TDP-43 FFLLEye, pan-neural, ubiquitary [8]
 TDP-43 CTFPan-neural, ubiquitary [8]
 TBPH F/L 150–152Pan-neural [19]
 hTDP-43mutNESEye, muscle, glia, pan-neural [18]
 hTDP-43mutNLSEye, muscle, glia, pan-neural [18]
TDP-43 T202 contained only the C-terminal domain (the N-terminal RRM motifs are lacking). TDP-43 ΔNLS lacked a functional nuclear localization signal. TDP-43 FFLL contained two missense mutations (F147L/F149L) into the first RNA recognition motif (RRM1) that abolished TDP-43 RNA-binding function [35]. TBPH F/L 150-152 contained point mutations of the two Phe > Leu in RNP-2 of RRM1 corresponding to human (F147L and F149L). TDP-43 CTF consisted in the C-terminal fragment (206–414) similar to those found in cytosolic aggregates of ALS/FTLD patients. TDP-43 NLS-mut and hTDP-43mutNLS were mutants in the nuclear localization sequence (NLS). TDP-43 NES-mut and hTDP-43mutNES were mutants in the nuclear export sequence (NES).