Côté, Patrice
http://hdl.handle.net/10222/22294
2024-03-29T01:53:01ZThe dystroglycan complex is necessary for stabilization of acetylcholine receptor
clusters at neuromuscular junctions and formation of the synaptic basement membrane
http://hdl.handle.net/10222/28772
The dystroglycan complex is necessary for stabilization of acetylcholine receptor
clusters at neuromuscular junctions and formation of the synaptic basement membrane
Jacobson, C.; Cote, Patrice D.; Rossi, SG; Rotundo, RL; Carbonetto, S.
The dystrophin-associated protein (DAP) complex spans the sarcolemmal membrane linking
the cytoskeleton to the basement membrane surrounding each myofiber. Defects in the DAP
complex have been linked previously to a variety of muscular dystrophies, Other evidence
points to a role for the DAP complex in formation of nerve-muscle synapses. We show that
myotubes differentiated from dystroglycan(-/-) embryonic stem cells are responsive to
agrin, but produce acetyl choline receptor (AChR) clusters which are two to three times
larger in area, about half as dense, and significantly less stable than those on
dystroglycan+/+ myotubes, AChRs at neuromuscular junctions are similarly affected in
dystroglycan-deficient chimeric mice and there is a coordinate increase in nerve
terminal size at these junctions. In culture and in vivo the absence of dystroglycan
disrupts the localization to AChR clusters of laminin, perlecan, and
acetylcholinesterase (AChE), but not rapsyn or agrin. Treatment of myotubes in culture
with laminin induces AChR clusters on dystroglycan+/+, but not -/- myotubes, These
results suggest that dystroglycan is essential for the assembly of a synaptic basement
membrane, most notably by localizing AChE through its binding to perlecan, In addition.
they suggest that dystroglycan functions in the organization and stabilization of AChR
clusters, which appear to be mediated through its binding of laminin.
2001-02-01T00:00:00ZReduced Retinal Function in the Absence of Na(v)1.6
http://hdl.handle.net/10222/28766
Reduced Retinal Function in the Absence of Na(v)1.6
Smith, Benjamin J.; Cote, Patrice D.
Background: Mice with a function-blocking mutation in the Scn8a gene that encodes
Na(v)1.6, a voltage-gated sodium channel (VGSC) isoform normally found in several types
of retinal neurons, have previously been found to display a profoundly abnormal dark
adapted flash electroretinogram. However the retinal function of these mice in light
adapted conditions has not been studied. Methodology/Principal Findings: In the present
report we reveal that during light adaptation these animals are shown to have
electroretinograms with significant decreases in the amplitude of the a-and b-waves. The
percent decrease in the a-and b-waves substantially exceeds the acute effect of VGSC
block by tetrodotoxin in control littermates. Intravitreal injection of CoCl2 or CNQX to
isolate the a-wave contributions of the photoreceptors in littermates revealed that at
high background luminance the cone-isolated component of the a-wave is of the same
amplitude as the a-wave of mutants. Conclusions/Significance: Our results indicate that
Scn8a mutant mice have reduced function in both rod and the cone retinal pathways. The
extent of the reduction in the cone pathway, as quantified using the ERG b-wave, exceeds
the reduction seen in control littermates after application of TTX, suggesting that a
defect in cone photoreceptors contributes to the reduction. Unless the postreceptoral
component of the a-wave is increased in Scn8a mutant mice, the reduction in the b-wave
is larger than can be accounted for by reduced photoreceptor function alone. Our data
suggests that the reduction in the light adapted ERG of Scn8a mutant mice is caused by a
combination of reduced cone photoreceptor function and reduced depolarization of cone ON
bipolar cells. This raises the possibility that Na(v)1.6 augments signaling in cone
bipolar cells.
2012-02-01T00:00:00Z