Disassembly of the cholinergic postsynaptic apparatus induced by axotomy in mouse sympathetic neurons: the loss of dystrophin and beta-dystroglycan immunoreactivity precedes that of the acetylcholine receptor.
In mouse sympathetic superior cervical ganglion (SCG), cortical cytoskeletal proteins such as dystrophin (Dys) and beta1sigma2 spectrin colocalize with beta-dystroglycan (beta-DG), a transmembrane dystrophin-associated protein, and the acetylcholine receptor (AChR) at the postsynaptic specialization. The function of the dystrophin-dystroglycan complex in the organization of the neuronal cholinergic postsynaptic apparatus was studied following changes in the immunoreactivity of these proteins during the disassembly and subsequent reassembly of the postsynaptic specializations induced by axotomy of the ganglionic neurons. After axotomy, a decrease in the number of intraganglionic synapses was observed (t1/2 8 h 45'), preceded by a rapid decline of postsynaptic specializations immunopositive for beta-DG, Dys, and alpha3 AChR subunit (alpha3AChR) (t1/2 3 h 45', 4 h 30' and 6 h, respectively). In contrast, the percentage of postsynaptic densities immunopositive for beta1sigma2 spectrin remained unaltered. When the axotomized neurons began to regenerate their axons, the number of intraganglionic synapses increased, as did that of postsynaptic specializations immunopositive for beta-DG, Dys, and alpha3AChR. The latter number increased more slowly than that of Dys and beta-DG. These observations suggest that in SCG neurons, the dystrophin-dystroglycan complex might play a role in the assembly-disassembly of the postsynaptic apparatus, and is probably involved in the stabilization of AChR clusters.
Zaccaria
M L
ML
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Roma, Italy.
De Stefano
M E
ME
Properzi
F
F
Gotti
C
C
Petrucci
T C
TC
Paggi
P
P
D000109:Acetylcholine / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000502:physiology; D019771:Axotomy; D003598:Cytoskeletal Proteins / Q000032:analysis; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D049030:Dystroglycans; D000109:Acetylcholine