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J. Cell Biol.,
Volume 145, Number 6, June 14, 1999 1325-1340
-Dystroglycan Is a Laminin Receptor Involved in Extracellular Matrix
Assembly on Myotubes and Muscle Cell Viability
* Center for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, Montreal,
Quebec H3G 1A4, Canada; and Chromos Molecular Systems, Inc., Burnaby, British Columbia V5A 1W9, Canada
-Dystroglycan (-DG) is a laminin-binding
protein and member of a glycoprotein complex associated with dystrophin that has been implicated in the etiology of several muscular dystrophies. To study the
function of DG, C2 myoblasts were transfected stably with an antisense DG expression construct. Myotubes
from two resulting clones (11F and 11E) had at least a
40-50% and 80-90% reduction, respectively, in -DG
but normal or near normal levels of -sarcoglycan, integrin 
1 subunit, acetylcholine receptors (AChRs), and
muscle-specific kinase (MuSK) when compared with
parental C2 cells or three clones (11A, 9B, and 10C)
which went through the same transfection and selection
procedures but expressed normal levels of -DG. Antisense DG-expressing myoblasts proliferate at the same
rate as parental C2 cells and differentiate into myotubes, however, a gradual loss of cells was observed in
these cultures. This loss correlates with increased apoptosis as indicated by greater numbers of nuclei with
condensed chromatin and more nuclei labeled by the
TUNEL method. Moreover, there was no sign of increased membrane permeability to Trypan blue as
would be expected with necrosis. Unlike parental C2
myotubes, 11F and 11E myotubes had very little laminin (LN) on their surfaces; LN instead tended to accumulate on the substratum between myotubes. Exogenous LN bound to C2 myotubes and was redistributed into plaques along with -DG on their surfaces but far
fewer LN/-DG plaques were seen after LN addition to
11F or 11E myotubes. These results suggest that -DG
is a functional LN receptor in situ which is required for
deposition of LN on the cell and, further, implicate
-DG in the maintenance of myotube viability.
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