Silencing of NHERF-2 abolishes muscarinic-mediated translocation of
PMCA. NHERF-2 was silenced in HT-29 cells using siRNA plasmids Shag-FF
(vector control) and Shag-274 or Shag-361, exposed to ACh (10
μm), and cell surface biotinylation was used to determine
surface levels of PMCA and NHERF-2. A, representative Western blot
demonstrating silencing of NHERF-2. B, Shag-274 and Shag-361 reduced
endogenous NHERF-2 protein levels to 57 ± 5% and 54 ± 6%
(n = 3; **, p < 0.01). C,
representative Western blot showing endogenous NHERF-1 was not altered.
D, representative Western blot showing changes in membrane-associated
PMCA following muscarinic activation in HT-29 cells silenced for NHERF-2.
E, densitometry showing changes in membrane-associated PMCA during
muscarinic stimulation in NHERF-2 knock-down cells. The ACh-mediated insertion
of PMCA at 60 s was abolished. Furthermore, during stimulation the levels of
PMCA in silenced cells reduced at 120 s to 46 ± 5% (Shag-274) and 53
± 7% (Shag-361) compared with control (n = 3; ***,
p < 0.001). Data are expressed as mean ± S.E.