RyR1 carrying the E4032A mutation is properly expressed in 1B5
myotubes. 1B5 cells grown in collagen-coated 35-mm dishes were infected
with either RyR1 or E4032A cDNA-containing herpes simplex virus
amplicon virions at 3 × 105 IU/ml.
(A) Western blot of 1B5 myotube preparations expressing
E4032A-RyR1 (lane 1, 20 μg), 1B5 null myotubes not transduced with
cDNA (lane 2, 20 μg), and 1B5 myotubes expressing wtRyR1 (lane 4, 20
μg). Lane 3 contains 0.5 μg of rabbit junctional sarcoplasmic
reticulum as a positive control. (B) The intracellular
distribution of E4032A expressed in 1B5 myotubes was examined by using
immunocytochemistry as described in Materials and
Methods. E4032A was properly targeted to junctional domains at
the fiber periphery as indicated by the punctate appearance of the
immunolabeling pattern which was indistinguishable from the pattern
obtained when wtRyR1 was expressed in 1B5 cells (C).
(D and E) E4032A- and wtRyR1-expressing
1B5 myotubes were examined for DHPR tetrad formation by
freeze–fracture electron microscopy. Both RyRs induced tetrad
formation in the plasmalemma of 1B5 cells as indicated (arrows). The
tetrads were similar in appearance and indicate the formation of a
stereospecific link between four DHPRs and the four subunits of the
RyR.