title: Time lapse in vivo visualization of developmental stabilization of synaptic receptors at neuromuscular junctions.
abstract: The lifetime of nicotinic acetylcholine receptors (AChRs) in neuromuscular junctions (NMJs) is increased from <1 day to >1 week during early postnatal development. However, the exact timing of AChR stabilization is not known, and its correlation to the concurrent embryonic to adult AChR channel conversion, NMJ remodeling, and neuromuscular diseases is unclear. Using a novel time lapse in vivo imaging technology we show that replacement of the entire receptor population of an individual NMJ occurs end plate-specifically within hours. This makes it possible to follow directly in live animals changing stabilities of end plate receptors. In three different, genetically modified mouse models we demonstrate that the metabolic half-life values of synaptic AChRs increase from a few hours to several days after postnatal day 6. Developmental stabilization is independent of receptor subtype and apparently regulated by an intrinsic muscle-specific maturation program. Myosin Va, an F-actin-dependent motor protein, is also accumulated synaptically during postnatal development and thus could mediate the stabilization of end plate AChR.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
authors.forename: Pessah
authors.initials: P
authors.lastname: Yampolsky
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Pacifici
authors.forename: Lukas
authors.initials: L
authors.lastname: Lomb
authors.forename: Günter
authors.initials: G
authors.lastname: Giese
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Rudolf
authors.forename: Ira V
authors.initials: IV
authors.lastname: Röder
authors.forename: Veit
authors.initials: V
authors.lastname: Witzemann
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009045:Motor Endplate / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; C513082:Myo5a protein, mouse; D011978:Receptors, Nicotinic; D024701:Myosin Type V; D018995:Myosin Heavy Chains
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