Transepithelial Projections from Basal Cells Are Luminal Sensors in Pseudostratified Epithelia

Center for Systems Biology, Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell (Impact Factor: 32.24). 01/2009; 135(6):1108-17. DOI: 10.1016/j.cell.2008.10.020
Source: PubMed

ABSTRACT Basal cells are by definition located on the basolateral side of several epithelia, and they have never been observed reaching the lumen. Using high-resolution 3D confocal imaging, we report that basal cells extend long and slender cytoplasmic projections that not only reach toward the lumen but can cross the tight junction barrier in some epithelia of the male reproductive and respiratory tracts. In this way, the basal cell plasma membrane is exposed to the luminal environment. In the epididymis, in which luminal acidification is crucial for sperm maturation and storage, these projections contain the angiotensin II type 2 receptor (AGTR2). Activation of AGTR2 by luminal angiotensin II, increases proton secretion by adjacent clear cells, which are devoid of AGTR2. We propose a paradigm in which basal cells scan and sense the luminal environment of pseudostratified epithelia and modulate epithelial function by a mechanism involving crosstalk with other epithelial cells.

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Available from: Winnie Shum, Aug 26, 2015
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    • "Vertices of epithelial cells have been paid attention as the points supporting the tensile force of actomyosin along cell-cell junctions. Additionally, TCs are used as windows for protrusions of cells just beneath epithelial cellular sheets to sense the outer environment.32,45 tTJs may be involved in these phenomena directly or indirectly. "
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    ABSTRACT: When the apicolateral border of epithelial cells is compared with a polygon, its sides correspond to the apical junctional complex, where cell adhesion molecules assemble from the plasma membranes of two adjacent cells. On the other hand, its vertices correspond to tricellular contacts, where the corners of three cells meet. Vertebrate tricellular contacts have specialized structures of tight junctions, termed tricellular tight junctions (tTJs). tTJs were identified by electron microscopic observations more than 40 years ago, but have been largely forgotten in epithelial cell biology since then. The identification of tricellulin and angulin family proteins as tTJ-associated membrane proteins has enabled us to study tTJs in terms of not only the paracellular barrier function but also unknown characteristics of epithelial cell corners via molecular biological approaches.
    05/2014; 2(3):e28960. DOI:10.4161/tisb.28960
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    • "Narrow cells are also positive for V-ATPase, thus thought to participate in lumen acidification (Pietrement et al., 2006). In this scenario, it has been recently proposed that basal cells scan and sense the luminal environment of the epididymis, and participate in a cross-talk with other epithelial cells, thus regulating their functions (Shum et al., 2008). As shown in this work, the epididymides of cSrc null mice are small in size due to deficient development of their caudal regions. "
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    ABSTRACT: Changes that occur to mammalian sperm upon epididymal transit and maturation render these cells capable of moving progressively and capacitating. Signaling events leading to mammalian sperm capacitation depend on the modulation of proteins by phosphorylation and dephosphorylation cascades. Recent experiments have demonstrated that the Src family of kinases plays an important role in the regulation of these events. However, sperm from cSrc null mice display normal tyrosine phosphorylation associated with capacitation. We report here that, despite normal phosphorylation, sperm from cSrc null mice display a severe reduction in forward motility, and are unable to fertilize in vitro. Histological analysis of seminiferous tubules in the testes, caput and corpus epididymis do not reveal obvious defects. However, the cauda epididymis is significantly smaller, and expression of key transport proteins in the epithelial cells lining this region is reduced in cSrc null mice compared to wild type littermates. Although previously, we and others have shown the presence of cSrc in mature sperm from cauda epididymis, a closer evaluation indicates that this tyrosine kinase is not present in sperm from the caput epididymis, suggesting that this protein is acquired by sperm later during epididymal maturation. Consistent with this observation, cSrc is enriched in vesicles released by the epididymal epithelium known as epididymosomes. Altogether, these observations indicate that cSrc is essential for cauda epididymal development and suggest an essential role of this kinase in epididymal sperm maturation involving cSrc extracellular trafficking.
    Developmental Biology 06/2012; 369(1):43-53. DOI:10.1016/j.ydbio.2012.06.017 · 3.55 Impact Factor
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    • "muscle cells. In contrast, PDE5 was not found in the epididymal epithelium using two different approaches, although components of cGMP pathways and cGMP-mediated functions have been described in epididymal epithelial cells (Jaleel et al., 2002; Mewe et al., 2006a; Shum et al., 2008). Thus, PDE5 inhibition could constitute a pharmacological tool allowing to discriminate between cGMP effects in contractile and epithelial cells. "
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    ABSTRACT: Contractility of the peritubular smooth muscle layer ensures the transit of immotile spermatozoa through the epididymal duct to acquire their fertilizing capacity. Atrial natriuretic peptide (ANP) and nitric oxide (NO) affect contractility via cGMP signals that are controlled by phosphodiesterases (PDEs). Sildenafil inhibits the cGMP-hydrolyzing PDE5 and thereby promotes relaxation of smooth muscle cells. While sildenafil is increasingly used in young patients for the treatment of pulmonary hypertension, virtually no knowledge exists about PDEs in the epididymis. Western blotting, immunohistochemistry and RT-PCR analyses after laser capture microdissection localized PDE5 to smooth muscle cells, but not to epithelial cells, of the epididymal duct in man and rat. Sildenafil, ANP and NO significantly slowed spontaneous contractions of rat epididymal duct segments in organ bath studies. Sildenafil effects were additive to ANP and NO. Long-term exposure to sildenafil in vivo did not change the PDE5 expression or the observed contractility pattern with the rapid relaxing response toward ANP, NO and sildenafil. Data demonstrate that PDE5 is an important member of cGMP signaling pathways regulating the finely orchestrated process of epididymal duct contractility and suggest, however, that in the epididymis side effects of therapeutically used sildenafil are unlikely.
    Molecular and Cellular Endocrinology 02/2012; 349(2):145-53. DOI:10.1016/j.mce.2011.09.039 · 4.41 Impact Factor
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