title: Synaptogenetic mechanisms controlling postsynaptic differentiation of the neuromuscular junction are nerve-dependent in human and nerve-independent in mouse C2C12 muscle cultures.
abstract: Acetylcholinesterase (EC 3.1.1.7, AChE) is one of the components of the neuromuscular junction (NMJ). Its expression and targeting in the skeletal muscle fiber is therefore under the control of the mechanisms responsible for the formation of the highly complex structure of this synapse. Recently, it has been demonstrated that myotubes of the C2C12 mouse muscle cell line form highly differentiated pretzel-like postsynaptic accumulations of acetylcholine receptors (AChRs) in the complete absence of the nerve if they are cultured on the laminin coating. This finding questions previously stressed importance of the nerve-derived factors in NMJ synaptogenesis and therefore deserves additional testing. The aim of this paper was to test whether the reported nerve-independency can be demonstrated also in the cultured human muscle meaning that the findings on C2C12 cultures can be extrapolated also to the human muscle. In our experiments aneurally cultured human myotubes failed to form AChR clusters on its surface, no matter if they were grown on normal gelatine or laminin coating. However, when innervated by neurons extending from the rat embryonic spinal cord, human myotubes formed AChR clusters with elaborate topography but strictly on the areas contacted by the nerve. One can hypothesize that higher nerve dependency of the NMJ synaptogenesis in humans in comparison to other species reflects species-specific differences in the organization of movement. Humans have the highest "fractionation of movement" capacity which probably requests different, more nerve-controlled development of the motor system including nerve-restricted development of the neuromuscular contacts.
authors.affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Gajsek
authors.forename: Marko
authors.initials: M
authors.lastname: Jevsek
authors.forename: Tomaz
authors.initials: T
authors.lastname: Mars
authors.forename: Katarina
authors.initials: K
authors.lastname: Mis
authors.forename: Sergej
authors.initials: S
authors.lastname: Pirkmajer
authors.forename: Janez
authors.initials: J
authors.lastname: Brecelj
authors.forename: Zoran
authors.initials: Z
authors.lastname: Grubic
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D051379:Mice; D018613:Microscopy, Confocal; D009469:Neuromuscular Junction / Q000201:enzymology / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D013569:Synapses / Q000201:enzymology / Q000502:physiology*
chemical_list: D011950:Receptors, Cholinergic; D000110:Acetylcholinesterase