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

• Published in: The European journal of neuroscience 2015-02, Vol.41 (3), p.316-327
• Main Authors: Patra, Kalicharan, Lyons, David J., Bauer, Pavol, Hilscher, Markus M., Sharma, Swati, Leão, Richardson N., Kullander, Klas
• Format: Article
• Language: English
• Subjects: acetylcholine; Animals; Blotting, Western; Female; Imaging, Three-Dimensional; Immunohistochemistry; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Microelectrodes; Microscopy, Confocal; Miniature Postsynaptic Potentials - physiology; Motor Activity - physiology; Muscle, Skeletal - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuromuscular Junction - physiology; Neuronal Plasticity - physiology; peripheral nervous system; Receptors, Cholinergic - metabolism; RNA, Messenger - metabolism; SLC10A4; Spinal Cord - metabolism; synaptic transmission; Synaptic Vesicles - physiology; vesicular aminergic-associated transporter; vesicular content; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.12790

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. Here, we demonstrate a novel and potentially important role for SLC10A4 (or VAAT) in maintaining the structural integrity and transmission efficiency at the neuromuscular junction (NMJ). VaatKO NMJs display fragmented endplates and reduced synaptic plasticity but elevated levels of cholinergic receptor transcripts. Further studies on VAAT may provide a better understanding of synaptic physiology and treatment of neuromuscular diseases.