Summary: Development/Plasticity/Repair
Nicotinic Acetylcholine Receptor Stability at the NMJ
Deficient in -Syntrophin In Vivo
Isabel Martinez-Pena y Valenzuela,1* Chakib Mouslim,1* Marcelo Pires-Oliveira,1* Marvin E. Adams,3
Stanley C. Froehner,3 and Mohammed Akaaboune1,2
1Department of Molecular, Cellular and Developmental Biology and 2Program in Neuroscience, University of Michigan, Ann Arbor, Michigan 48109, and
3Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195
-Syntrophin ( -syn), a scaffold protein, links signaling molecules to the dystrophin­glycoprotein complex. Absence of -syn from the
DGC is known to lead to structurally aberrant neuromuscular junctions (NMJs) with few acetylcholine receptors (AChRs) clustered at
synaptic sites. Using -syn knock-out mice, we show that during the first postnatal week, -syn is not required for synapse formation.
However,atpostnatalday6(P6)­P7,thestructuralintegrityofthepostsynapticapparatusisaltered,theturnoverrateofAChRsincreases
significantly, and the number/density of AChRs is impaired. At the adult -syn /
NMJ, the turnover rate of AChRs is 4 times faster
than wild-type synapses, and most removed receptors are targeted to degradation as few AChRs recycled to synaptic sites. Biochemical
analyses show that in muscle cells of adult knock-out -syn mice, total AChRs and scaffold protein rapsyn are significantly reduced, the
89 kDa and 75 kDa isoforms of tyrosine phosphorylated -dystrobrevin ( -dbn) 1 (which are required for the maintenance and stability
of AChR in -dbn /
synapses) are barely detectable. Electroporation of GFP- -dbn1 in -syn /
muscle cells partially restored
receptor density, turnover rate, and the structural integrity of the postsynaptic apparatus, whereas expression of rapsyn-GFP failed to

Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago

Collections: Biology and Medicine