title: Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach.
abstract: Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC-IM) in the stomach and colon and ICC in the deep muscular plexus (ICC-DMP) of the small intestine. In the absence of ICC-IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC-IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse-associated proteins between nerve terminals and ICC-IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP-25 were detected. Synaptotagmin and SNAP-25-immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC-IM but not smooth muscle. W/W(V) mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC-IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP-25 were detected in W/W(V) tissues. In the absence of ICC-IM, synaptotagmin and SNAP-25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT-PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD-93 and PSD-95 in the stomach and expression levels of PSD-93 and PSD-95 were reduced in W/W(V) mutants. These data support the existence of synaptic specializations between enteric nerves and ICC-IM in gastric tissues. In the absence of ICC-IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals.
authors.affiliation: Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
authors.forename: Elizabeth A H
authors.initials: EA
authors.lastname: Beckett
authors.forename: Yukari
authors.initials: Y
authors.lastname: Takeda
authors.forename: Haruko
authors.initials: H
authors.lastname: Yanase
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Sean M
authors.initials: SM
authors.lastname: Ward
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D017615:Enteric Nervous System / Q000502:physiology / Q000648:ultrastructure*; D005769:Gastrointestinal Motility / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure*; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology / Q000648:ultrastructure*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology / Q000648:ultrastructure*; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D050765:Qa-SNARE Proteins / Q000378:metabolism; D013270:Stomach / Q000294:innervation / Q000648:ultrastructure*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure*; D013572:Synaptic Vesicles / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050857:Synaptotagmins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; C033652:postsynaptic density proteins; D050857:Synaptotagmins