title: Synaptic Effects of Munc18-1 Alternative Splicing in Excitatory Hippocampal Neurons.
abstract: The munc18-1 gene encodes two splice-variants that vary at the C-terminus of the protein and are expressed at different levels in different regions of the adult mammalian brain. Here, we investigated the expression pattern of these splice variants within the brainstem and tested whether they are functionally different. Munc18-1a is expressed in specific nuclei of the brainstem including the LRN, VII and SOC, while Munc18-1b expression is relatively low/absent in these regions. Furthermore, Munc18-1a is the major splice variant in the Calyx of Held. Synaptic transmission was analyzed in autaptic hippocampal munc18-1 KO neurons re-expressing either Munc18-1a or Munc18-1b. The two splice variants supported synaptic transmission to a similar extent, but Munc18-1b was slightly more potent in sustaining synchronous release during high frequency stimulation. Our data suggest that alternative splicing of Munc18-1 support synaptic transmission to a similar extent, but could modulate presynaptic short-term plasticity.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam and VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Meijer
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam and VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Tony
authors.initials: T
authors.lastname: Cijsouw
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam and VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Ruud F
authors.initials: RF
authors.lastname: Toonen
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam and VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D051938:Munc18 Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D055366:Synaptic Potentials
chemical_list: D051938:Munc18 Proteins