NK receptors, Substance P, Ano1 expression and ultrastructural features of the muscle coat in Cav-1 -/- mouse ileum

G. Cipriani, Crenguta S. Serboiu, Mihaela Gherghiceanu, Maria Simonetta Faussone-Pellegrini, Maria Giuliana Vannucchi

Research output: Contribution to journalArticlepeer-review

Abstract

Caveolin (Cav)-1 is an integral membrane protein of caveolae playing a crucial role in various signal transduction pathways. Caveolae represent the sites for calcium entry and storage especially in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Cav-1 -/- mice lack caveolae and show abnormalities in pacing and contractile activity of the small intestine. Presently, we investigated, by transmission electron microscopy (TEM) and immunohistochemistry, whether the absence of Cav-1 in Cav-1 -/- mouse small intestine affects ICC, SMC and neuronal morphology, the expression of NK1 and NK2 receptors, and of Ano1 (also called Dog1 or TMEM16A), an essential molecule for slow wave activity in gastrointestinal muscles. ICC were also labelled with c-Kit and tachykinergic neurons with Substance P (SP). In Cav-1 -/- mice: (i) ICC were Ano1-negative but maintained c-Kit expression, (ii) NK1 and NK2 receptor immunoreactivity was more intense and, in the SMC, mainly intracytoplasmatic, (iii) SP-immunoreactivity was significantly reduced. Under TEM: (i) ICC, SMC and telocytes lacked typical caveolae but had few and large flask-shaped vesicles we called large-sized caveolae; (ii) SMC and ICC contained an extraordinary high number of mitochondria, (iii) neurons were unchanged. To maintain intestinal motility, loss of caveolae and reduced calcium availability in Cav-1-knockout mice seem to be balanced by a highly increased number of mitochondria in ICC and SMC. Loss of Ano-1 expression, decrease of SP content and consequently overexpression of NK receptors suggest that all these molecules are Cav-1-associated proteins.

Original languageEnglish (US)
Pages (from-to)2411-2420
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Caveolae
  • Caveolin-1
  • Electron microscopy
  • Immunohistochemistry
  • Interstitial cells of Cajal
  • NK1 and NK2 receptors
  • Smooth muscle cells
  • Substance P
  • TMEM16A or ANO1 or DOG1

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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