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Expression and function of NIK- and IKK2-binding protein (NIBP) in mouse enteric nervous system.

ABSTRACT: NIK- and IKK2-binding protein (NIBP)/TRAPPC9 is expressed in brain neurons, and human NIBP mutations are associated with neurodevelopmental disorders. The cellular distribution and function of NIBP in the enteric nervous system (ENS) remain unknown.Western blot and reverse transcription-polymerase chain reaction analysis were used respectively to identify the protein and mRNA expression of NIBP and other neuronal markers. Multi-labeled immunofluorescent microscopy and confocal image analysis were used to examine the cellular distribution of NIBP-like immunoreactivity (IR) in whole mount intestine. Enteric neuronal cell line (ENC) was infected with lentivirus carrying NIBP or its shRNA expression vectors and treated with vehicle or tumor necrosis factor (TNF)?.NIBP is expressed at both mRNA and protein levels in different regions and layers of the mouse intestine. NIBP-like-IR was co-localized with various neuronal markers, but not with glial, smooth muscular, or interstitial cells of Cajal markers. A small population of NIBP-expressing cells and fibers in extra-ganglionic and intra-ganglionic area were negative for pan-neuronal markers HuD or Peripherin. Relatively high NIBP-like-IR was found in 35-44% of myenteric neurons and 9-10% of submucosal neurons. Approximately 98%, 87%, and 43% of these relatively high NIBP-expressing neurons were positive for choline acetyltransferase, neuronal nitric oxide synthase and Calretinin, respectively. NIBP shRNA knockdown in ENC inhibited TNF?-induced NF?B activation and neuronal differentiation, whereas NIBP overexpression promoted it.NIBP is extensively expressed in the ENS with relatively high level in a subpopulation of enteric neurons. Various NIBP expression levels in different neurons may represent dynamic trafficking or posttranslational modification of NIBP in some functionally active neurons and ultimately regulate ENS plasticity.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC3962790 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Expression and function of NIK- and IKK2-binding protein (NIBP) in mouse enteric nervous system.

Zhang Y Y Bitner D D Pontes Filho A A AA Li F F Liu S S Wang H H Yang F F Adhikari S S Gordon J J Srinivasan S S Hu W W

Neurogastroenterology and motility 20130909 1

<h4>Background</h4>NIK- and IKK2-binding protein (NIBP)/TRAPPC9 is expressed in brain neurons, and human NIBP mutations are associated with neurodevelopmental disorders. The cellular distribution and function of NIBP in the enteric nervous system (ENS) remain unknown.<h4>Methods</h4>Western blot and reverse transcription-polymerase chain reaction analysis were used respectively to identify the protein and mRNA expression of NIBP and other neuronal markers. Multi-labeled immunofluorescent microsc ...[more]

PMID: 24011459

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Project description:BackgroundCa(2+)/calmodulin-dependent protein kinases (CaMKs) are major downstream mediators of neuronal calcium signaling that regulate multiple neuronal functions. CaMKII, one of the key CaMKs, plays a significant role in mediating cellular responses to external signaling molecules. Although calcium signaling plays an essential role in the enteric nervous system (ENS), the role of CaMKII in neurogenic intestinal function has not been determined. In this study, we investigated the function and expression pattern of CaMKII in the ENS across several mammalian species.Methodology/principal findingsCaMKII expression was characterized by immunofluorescence analyses and Western Blot. CaMKII function was examined by intracellular recordings and by assays of colonic contractile activity. Immunoreactivity for CaMKII was detected in the ENS of guinea pig, mouse, rat and human preparations. In guinea pig ENS, CaMKII immunoreactivity was enriched in both nitric oxide synthase (NOS)- and calretinin-containing myenteric plexus neurons and non-cholinergic secretomotor/vasodilator neurons in the submucosal plexus. CaMKII immunoreactivity was also expressed in both cholinergic and non-cholinergic neurons in the ENS of mouse, rat and human. The selective CaMKII inhibitor, KN-62, suppressed stimulus-evoked purinergic slow EPSPs and ATP-induced slow EPSP-like response in guinea pig submucosal plexus, suggesting that CaMKII activity is required for some metabotropic synaptic transmissions in the ENS. More importantly, KN-62 significantly suppressed tetrodotoxin-induced contractile response in mouse colon, which suggests that CaMKII activity is a major determinant of the tonic neurogenic inhibition of this tissue.ConclusionENS neurons across multiple mammalian species express CaMKII. CaMKII signaling constitutes an important molecular mechanism for controlling intestinal motility and secretion by regulating the excitability of musculomotor and secretomotor neurons. These findings revealed a fundamental role of CaMKII in the ENS and provide clues for the treatment of intestinal dysfunctions.

Dataset Information

Expression and function of NIK- and IKK2-binding protein (NIBP) in mouse enteric nervous system.

Publications

Expression and function of NIK- and IKK2-binding protein (NIBP) in mouse enteric nervous system.

Similar Datasets

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