title: Formation of cholinergic synapse-like specializations at developing murine muscle spindles.
abstract: Muscle spindles are complex stretch-sensitive mechanoreceptors. They consist of specialized skeletal muscle fibers, called intrafusal fibers, which are innervated in the central (equatorial) region by afferent sensory axons and in both polar regions by efferent γ-motoneurons. We show that AChRs are concentrated at the γ-motoneuron endplate as well as in the equatorial region where they colocalize with the sensory nerve ending. In addition to the AChRs, the contact site between sensory nerve ending and intrafusal muscle fiber contains a high concentration of choline acetyltransferase, vesicular acetylcholine transporter and the AChR-associated protein rapsyn. Moreover, bassoon, a component of the presynaptic cytomatrix involved in synaptic vesicle exocytosis, is present in γ-motoneuron endplates but also in the sensory nerve terminal. Finally, we demonstrate that during postnatal development of the γ-motoneuron endplate, the AChR subunit stoichiometry changes from the γ-subunit-containing fetal AChRs to the ε-subunit-containing adult AChRs, similar and approximately in parallel to the postnatal subunit maturation at the neuromuscular junction. In contrast, despite the onset of ε-subunit expression during postnatal development the γ-subunit remains detectable in the equatorial region by subunit-specific antibodies as well as by analysis of muscle spindles from mice with genetically-labeled AChR γ-subunits. These results demonstrate an unusual maturation of the AChR subunit composition at the annulospiral endings and suggest that in addition to the recently described glutamatergic secretory system, the sensory nerve terminals are also specialized for cholinergic synaptic transmission, synaptic vesicle storage and exocytosis.
authors: Department of Physiological Genomics, Ludwig-Maximilians-University, Pettenkoferstrasse 12, D-80336 Munich, Germany; Helmholtz Center Munich, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
authors: Yina
authors: Y
authors: Zhang
authors: Department of Physiological Genomics, Ludwig-Maximilians-University, Pettenkoferstrasse 12, D-80336 Munich, Germany.
authors: Marta
authors: M
authors: Wesolowski
authors: Department of Physiological Genomics, Ludwig-Maximilians-University, Pettenkoferstrasse 12, D-80336 Munich, Germany.
authors: Andromachi
authors: A
authors: Karakatsani
authors: Max Planck Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany.
authors: Veit
authors: V
authors: Witzemann
authors: Department of Physiological Genomics, Ludwig-Maximilians-University, Pettenkoferstrasse 12, D-80336 Munich, Germany. Electronic address: skroeger@lmu.de.
authors: Stephan
authors: S
authors: Kröger
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000493:pharmacokinetics; D005089:Exocytosis / Q000502:physiology; D049452:Green Fluorescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009045:Motor Endplate / Q000378:metabolism; D009047:Motor Neurons, Gamma / Q000502:physiology; D024510:Muscle Development; D009124:Muscle Proteins / Q000493:pharmacokinetics; D009470:Muscle Spindles / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000493:pharmacokinetics; D009469:Neuromuscular Junction / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D050494:Vesicular Acetylcholine Transport Proteins / Q000493:pharmacokinetics
chemical_list: C498441:Bsn protein, mouse; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D050494:Vesicular Acetylcholine Transport Proteins; C051609:peripheral membrane protein 43K; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase
keywords: Acetylcholine receptor; Annulospiral ending, γ-motoneuron; Bassoon; Muscle spindle; Proprioception; Synaptogenesis