Expression of Myc-TDP-43-ΔNLS mutants results in the
sequestration of ubiquitinated and insoluble endogenous TDP-43. QBI-293
cells 24 h (A), or 72 h (B) post-transfection with empty
vector (CTRL), Myc-TDP-43-WT (WT), Myc-TDP-43-ΔNLS1
(ΔNLS1), Myc-TDP-43-ΔNLS2 (ΔNLS2), or
Myc-TDP-43-ΔNLS1/2 (ΔNLS1/2) sequentially extracted with
RIPA (R) and urea buffer (U). Immunoblotting was conducted
with TDP-43 antibody. Myc-TDP-43 (Myc) migrates slower than
endogenous TDP-43 (Endo). Over-exposure of the immunoblot
demonstrates the presence of a high Mr smear
(**) and C-terminal fragments (*) in the urea fractions
of Myc-TDP-43-NLS mutants in transfected cells. α-Tubulin was used as a
loading control. C, immunoblots (IB) of immunoprecipitated
(IP) QBI-293 cell lysates cotransfected with empty vector,
Myc-TDP-43-WT, or Myc-TDP-43-ΔNLS1/2 and HA-tagged ubiquitin
(HA-Ub) in the presence (+LAC) or absence of LAC. Note the
presence of the LAC-dependent, ubiquitinated TDP-43 positive
high-Mr smear and the TDP-43 C-terminal fragments.