Abstract
To elucidate the efferent functions of sensory nerve endings, the distribution of calretinin and vesicular glutamate transporter 1 (VGLUT1) in laryngeal laminar nerve endings and the immunohistochemical distribution of proteins associated with synaptic vesicle release, i.e., t-SNARE (SNAP25 and syntaxin 1), v-SNARE (VAMP1 and VAMP2), synaptotagmin 1 (Syt1), bassoon, and piccolo, were examined. Subepithelial laminar nerve endings immunoreactive for Na+-K+-ATPase α3-subunit (NKAα3) were largely distributed in the whole-mount preparation of the epiglottic mucosa, and several endings were also immunoreactive for calretinin. VGLUT1 immunoreactivity was observed within terminal part near the outline of the small processes of NKAα3-immunoreactive nerve ending. SNAP25, syntaxin 1, and VAMP1 immunoreactivities were detected in terminal parts of calretinin-immunoreactive endings, whereas VAMP2 immunoreactivity was only observed in a few terminals. Terminal parts immunoreactive for calretinin and/or VGLUT1 also exhibited immunoreactivities for Syt1, Ca2+ sensor for membrane trafficking, and for bassoon and piccolo, presynaptic scaffold proteins. The presence of vesicular release-related proteins, including SNARE proteins, in the terminals of laryngeal laminar endings indicate that intrinsic glutamate modulates their afferent activity in an autocrine-like manner.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study are included in this published article. Additional information is available from the corresponding author upon reasonable request.
References
Arystarkhova E, Sweadner KJ (1996) Isoform-specific monoclonal antibodies to Na, K-ATPase alpha subunits. Evidence for a tissue-specific post-translational modification of the alpha subunit. J Biol Chem 271:23407–23417. https://doi.org/10.1074/jbc.271.38.23407
Banks RW, Cahusac PMB, Graca A, Kain N, Shenton F, Singh P, Njå A, Simon A, Watson S, Slater CR, Bewick GS (2013) Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles. J Physiol 591:2523–2540. https://doi.org/10.1113/jphysiol.2012.243659
Barnstable CJ, Hofstein R, Akagawa K (1985) A marker of early amacrine cell development in rat retina. Brain Res 352:286–290. https://doi.org/10.1016/0165-3806(85)90116-6
Bersier MG, Peña C, Arnaiz GR (2011) Changes in Na+, K+-ATPase activity and alpha 3 subunit expression in CNS after administration of Na+, K+-ATPase inhibitors. Neurochem Res 36:297–303. https://doi.org/10.1007/s11064-010-0317-x
Bewick GS, Reid B, Richardson C, Banks RW (2005) Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic-like vesicles: evidence from the rat muscle spindle primary sensory ending. J Physiol 562:381–394. https://doi.org/10.1113/jphysiol.2004.074799
Brouns I, de Proost I, Pintelon I, Timmermans JP, Adriaensen D (2006) Sensory receptors in the airways: neurochemical coding of smooth muscle-associated airway receptors and pulmonary neuroepithelial body innervation. Auton Neurosci 126–127:307–319. https://doi.org/10.1016/j.autneu.2006.02.006
Cahusac PMB, Senok SS (2006) Metabotropic glutamate receptor antagonists selectively enhance responses of slowly adapting type I mechanoreceptors. Synapse 59:235–242. https://doi.org/10.1002/syn.20236
Cahusac PMB, Senok SS, Hitchcock IS, Genever PG, Baumann KI (2005) Are unconventional NMDA receptors involved in slowly adapting type I mechanoreceptor responses? Neuroscience 133:763–773. https://doi.org/10.1016/j.neuroscience.2005.03.018
Carr CM, Munson M (2007) Tag team action at the synapse. EMBO Rep 8:834–838. https://doi.org/10.1038/sj.embor.7401051
Cooper AP, Gillespie DC (2011) Synaptotagmins I and II in the developing rat auditory brainstem: synaptotagmin I is transiently expressed in glutamate- releasing immature inhibitory terminals. J Comp Neurol 519:2417–2433. https://doi.org/10.1002/cne.22634
Cupertino RB, Kappel DB, Bandeira CE, Schuch JB, da Silva BS, Müller D, Bau CHD, Mota NR (2016) SNARE complex in developmental psychiatry: neurotransmitter exocytosis and beyond. J Neural Transm (Vienna) 123:867–883. https://doi.org/10.1007/s00702-016-1514-9
Fox MA, Sanes JR (2007) Synaptotagmin I and II are present in distinct subsets of central synapses. J Comp Neurol 503:280–296. https://doi.org/10.1002/cne.21381
Grassmeyer JJ, Cahill AL, Hays CL, Barta C, Quadros RM, Gurumurthy CB, Thoreson WB (2019) Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors. eLife 8:e45946. https://doi.org/10.7554/eLife.45946
Han J, Pluhackova K, Böckmann RA (2017) The multifaceted role of SNARE proteins in membrane fusion. Front Physiol 8:5. https://doi.org/10.3389/fphys.2017.00005
Holt M, Varoqueaux F, Wiederhold K, Takamori S, Urlaub H, Fasshauer D, Jahn R (2006) Identification of SNAP-47, a novel Qbc-SNARE with ubiquitous expression. J Biol Chem 281:17076–17083. https://doi.org/10.1074/jbc.M513838200
Honer WG, Hu L, Davies P (1993) Human synaptic proteins with a heterogeneous distribution in cerebellum and visual cortex. Brain Res 609:9–20. https://doi.org/10.1016/0006-8993(93)90848-h
Honma S, Taki K, Lei S, Niwa H, Wakisaka S (2010) Immunohistochemical localization of SNARE proteins in dental pulp and periodontal ligament of the rat incisor. Anat Rec 293:1070–1080. https://doi.org/10.1002/ar.21106
Honma S, Kato A, Shi L, Yatani H, Wakisaka S (2012) Vesicular glutamate transporter immunoreactivity in the periodontal ligament of the rat incisor. Anat Rec 295:160–166. https://doi.org/10.1002/ar.21465
Jahn R, Scheller RH (2006) SNAREs—engines for membrane fusion. Nat Rev Mol Cell Biol 7:631–643. https://doi.org/10.1038/nrm2002
Johnson J, Fremeau RT Jr, Duncan JL, Rentería RC, Yang H, Hua Z, Liu X, LaVail MM, Edwards RH, Copenhagen DR (2007) Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions. J Neurosci 27:7245–7255. https://doi.org/10.1523/JNEUROSCI.0815-07.2007
Kim SH, Ryan TA (2013) Balance of calcineurin Aα and CDK5 activities sets release probability at nerve terminals. J Neurosci 33:8937–8950. https://doi.org/10.1523/JNEUROSCI.4288-12.2013
Kohno R, Toyono T, Seta Y, Kataoka S, Yamaguchi K, Toyoshima K (2005) Expression of synaptotagmin 1 in the taste buds of rat gustatory papillae. Arch Histol Cytol 68:235–241. https://doi.org/10.1679/aohc.68.235
Krauhs JM (1979) Structure of rat aortic baroreceptors and their relationship to connective tissue. J Neurocytol 8:401–414. https://doi.org/10.1007/BF01214800
Li JY, Jahn R, Dahlström A (1994) Synaptotagmin I is present mainly in autonomic and sensory neurons of the rat peripheral nervous system. Neuroscience 63:837–850. https://doi.org/10.1016/0306-4522(94)90528-2
Liu C, Kershberg L, Wang J, Schneeberger S, Kaeser PS (2018) Dopamine secretion is mediated by sparse active zone-like release sites. Cell 172:706–718. https://doi.org/10.1016/j.cell.2018.01.008
Masuda H, Nakamuta N, Yamamoto Y (2019) Morphology of GNAT3-immunoreactive chemosensory cells in the rat larynx. J Anat 234:149–164. https://doi.org/10.1111/joa.12914
Matsuoka H, Harada K, Nakamura J, Fukuda M, Inoue M (2011) Differential distribution of synaptotagmin-1, -4, -7, and -9 in rat adrenal chromaffin cells. Cell Tissue Res 344:41–50. https://doi.org/10.1007/s00441-011-1131-8
Matthew WD, Tsavaler L, Reichardt LF (1981) Identification of a synaptic vesicle-specific membrane protein with a wide distribution in neuronal and neurosecretory tissue. J Cell Biol 91:257–269. https://doi.org/10.1083/jcb.91.1.257
Mukherjee K, Yang X, Gerber SH, Kwon HB, Ho A, Castillo PE, Liu X, Südhof TC (2010) Piccolo and bassoon maintain synaptic vesicle clustering without directly participating in vesicle exocytosis. Proc Natl Acad Sci USA 107:6504–6509. https://doi.org/10.1073/pnas.1002307107
Ovsepian Sv, Dolly JO (2011) Dendritic SNAREs add a new twist to the old neuron theory. Proc Natl Acad Sci USA 108:19113–19120. https://doi.org/10.1073/pnas.1017235108
Parpura V, Mohideen U (2008) Molecular form follows function: (un)snaring the SNAREs. Trends Neurosci 31:435–443. https://doi.org/10.1016/j.tins.2008.06.003
Pintelon I, Brouns I, de Proost I, van Meir F, Timmermans JP, Adriaensen D (2007) Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts. Am J Respir Cell Mol Biol 36:541–551. https://doi.org/10.1165/rcmb.2006-0256OC
Ravichandran V, Chawla A, Roche PA (1996) Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues. J Biol Chem 271:13300–13303. https://doi.org/10.1074/jbc.271.23.13300
Sant’Ambrogio G, Tsubone H, Sant’Ambrogio FB (1995) Sensory information from the upper airway: role in the control of breathing. Respir Physiol 102:1–16. https://doi.org/10.1016/0034-5687(95)00048-i
Schwaller B (2014) Calretinin: from a “simple” Ca2+ buffer to a multifunctional protein implicated in many biological processes. Front Neuroanat 8:3. https://doi.org/10.3389/fnana.2014.00003
Sekizawa S, Tsubone H (1991) The respiratory activity of the superior laryngeal nerve in the rat. Respir Physiol 86:355–368. https://doi.org/10.1016/0034-5687(91)90106-s
Soda Y, Yamamoto Y (2012) Morphology and chemical characteristics of subepithelial laminar nerve endings in the rat epiglottic mucosa. Histochem Cell Biol 138:25–39. https://doi.org/10.1007/s00418-012-0939-y
Steegmaier M, Yang B, Yoo JS, Huang B, Shen M, Yu S, Luo Y, Scheller RH (1998) Three novel proteins of the syntaxin/SNAP-25 family. J Biol Chem 273:34171–34179. https://doi.org/10.1074/jbc.273.51.34171
Takahashi N, Nakamuta N, Yamamoto Y (2016) Morphology of P2X3-immunoreactive nerve endings in the rat laryngeal mucosa. Histochem Cell Biol 145:131–146. https://doi.org/10.1007/s00418-015-1371-x
Than K, Kim E, Navarro C, Chu S, Klier N, Occiano A, Ortiz S, Salazar A, Valdespino SR, Villegas NK, Wilkinson KA (2021) Vesicle-released glutamate is necessary to maintain muscle spindle afferent excitability but not dynamic sensitivity in adult mice. J Physiol 599:2953–2967. https://doi.org/10.1113/JP281182
Tom Dieck S, Sanmartí-Vila L, Langnaese K, Richter K, Kindler S, Soyke A, Wex H, Smalla KH, Kämpf U, Fränzer JT, Stumm M, Garner CC, Gundelfinger ED (1998) Bassoon, a novel zinc-finger CAG/glutamine-repeat protein selectively localized at the active zone of presynaptic nerve terminals. J Cell Biol 142:499–509. https://doi.org/10.1083/jcb.142.2.499
Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, Takei K, Matsui H (2002) Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J Neurosci 22:2590–2597. https://doi.org/10.1523/JNEUROSCI.22-07-02590.2002
Trimble WS, Cowan DM, Scheller RH (1988) VAMP-1: a synaptic vesicle-associated integral membrane protein. Proc Natl Acad Sci USA 85:4538–4542. https://doi.org/10.1073/pnas.85.12.4538
Urbina FL, Gupton SL (2020) SNARE-mediated exocytosis in neuronal development. Front Mol Neurosci 13:133. https://doi.org/10.3389/fnmol.2020.00133
Verkhratsky A, Fernyhough P (2014) Calcium signalling in sensory neurones and peripheral glia in the context of diabetic neuropathies. Cell Calcium 56:362–371. https://doi.org/10.1016/j.ceca.2014.07.005
Washbourne P, Schiavo G, Montecucco C (1995) Vesicle-associated membrane protein-2 (synaptobrevin-2) forms a complex with synaptophysin. Biochem J 305:721–724. https://doi.org/10.1042/bj3050721
Winsky L, Isaacs KR, Jacobowitz DM (1996) Calretinin mRNA and immunoreactivity in the medullary reticular formation of the rat: colocalization with glutamate receptors. Brain Res 741:123–133. https://doi.org/10.1016/s0006-8993(96)00908-0
Wolfes AC, Dean C (2020) The diversity of synaptotagmin isoforms. Curr Opin Neurobiol 63:198–209. https://doi.org/10.1016/j.conb.2020.04.006
Wu D, Bacaj T, Morishita W, Goswami D, Arendt KL, Xu W, Chen L, Malenka RC, Südhof TC (2017) Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP. Nature 544:316–321. https://doi.org/10.1038/nature21720
Yamamori S, Itakura M, Sugaya D, Katsumata O, Sakagami H, Takahashi M (2011) Differential expression of SNAP-25 family proteins in the mouse brain. J Comp Neurol 519:916–932. https://doi.org/10.1002/cne.22558
Yamamoto Y, Taniguchi K (2005) Immunolocalization of VR1 and VRL1 in rat larynx. Auton Neurosci 117:62–65. https://doi.org/10.1016/j.autneu.2004.11.003
Yamamoto Y, Atoji Y, Kuramoto H, Suzuki Y (1998) Calretinin-immunoreactive laminar nerve endings in the laryngeal mucosa of the rat. Cell Tissue Res 292:613–617. https://doi.org/10.1007/s004410051091
Yamamoto Y, Atoji Y, Suzuki Y (2000) Calbindin D28k-immunoreactive afferent nerve endings in the laryngeal mucosa. Anat Rec 259:237–247. https://doi.org/10.1002/1097-0185(20000701)259:3%3c237::AID-AR20%3e3.0.CO;2-P
Yokoyama T, Settai K, Nakamuta N, Yamamoto Y (2020) Vesicular glutamate transporter 2-immunoreactive afferent nerve terminals in rat carotid sinus baroreceptors. Acta Histochem 122:151469. https://doi.org/10.1016/j.acthis.2019.151469
Author information
Authors and Affiliations
Contributions
Y.Y. designed the study. Y.Y., H.M., and T.Y. acquired and analyzed the data. Y.Y. wrote the manuscript. T.Y. and N.N. critically revised the manuscript. All authors approved the article.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
Animal experimental protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of Iwate University (approval number: A201902).
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yamamoto, Y., Moriai, H., Yokoyama, T. et al. Immunohistochemical distribution of proteins involved in glutamate release in subepithelial sensory nerve endings of rat epiglottis. Histochem Cell Biol 157, 51–63 (2022). https://doi.org/10.1007/s00418-021-02038-0
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-021-02038-0