title: A role for solute carrier family 10 member 4, or vesicular aminergic-associated transporter, in structural remodelling and transmitter release at the mouse neuromuscular junction.
abstract: The solute carrier and presynaptic vesicle protein solute carrier family 10 member 4, or vesicular aminergic-associated transporter (VAAT), was recently proven to have a modulatory role in central cholinergic signalling. It is currently unknown whether VAAT also affects peripheral cholinergic synapses. Here we demonstrated a regulatory role for the presynaptic vesicle protein VAAT in neuromuscular junction (NMJ) development and function. NMJs lacking VAAT had fewer branch points, whereas endplates showed an increased number of islands. Whereas the amplitude of spontaneous miniature endplate potentials in VAAT-deficient NMJs was decreased, the amplitude of evoked endplate potentials and the size of the readily releasable pool of vesicles were both increased. Moreover, VAAT-deficient NMJs displayed aberrant short-term synaptic plasticity with enhanced synaptic depression in response to high-frequency stimulation. Finally, the transcript levels of cholinergic receptor subunits in VAAT-deficient muscles were increased, indicating a compensatory postsynaptic sensitization. Our results suggested that VAAT modulates NMJ transmission efficiency and, as such, may represent a novel target for treatment of disorders affecting motor neurons.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Kalicharan
authors.initials: K
authors.lastname: Patra
authors.forename: David J
authors.initials: DJ
authors.lastname: Lyons
authors.forename: Pavol
authors.initials: P
authors.lastname: Bauer
authors.forename: Markus M
authors.initials: MM
authors.lastname: Hilscher
authors.forename: Swati
authors.initials: S
authors.lastname: Sharma
authors.forename: Richardson N
authors.initials: RN
authors.lastname: Leão
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008839:Microelectrodes; D018613:Microscopy, Confocal; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D027981:Symporters; D013572:Synaptic Vesicles / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; C000601541:SLC10A4 protein, mouse; D027981:Symporters; D033921:Vesicular Transport Proteins
keywords: SLC10A4; acetylcholine; peripheral nervous system; synaptic transmission; vesicular aminergic-associated transporter; vesicular content