Differentiation of columnar epithelia: the hensin pathway

Vijayakumar, Soundarapandian; Takito, Jiro; Gao, Xiao Bo; Schwartz, George J.; Al‐Awqati, Qais

doi:10.1242/jcs.03269

Cited by 21 publications

(14 citation statements)

References 26 publications

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“…Further, treatment of these and other gp340-expressing cell lines with trypsin following viral pulsing does not ablate their abilities to maintain and transmit virus. Interestingly, the rabbit orthologue of gp340 functions as a modulator of polarity in epithelial cells (48,49). While a polarity reversal function for human gp340 has yet to be demonstrated, it remains a distinct possibility, given our finding that gp340 mediates transcytosis.…”

Section: Discussionmentioning

confidence: 85%

gp340 Promotes Transcytosis of Human Immunodeficiency Virus Type 1 in Genital Tract-Derived Cell Lines and Primary Endocervical Tissue

Stoddard

Cannon

et al. 2009

J Virol

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The human scavenger receptor gp340 has been identified as a binding protein for the human immunodeficiency virus type 1 (HIV-1) envelope that is expressed on the cell surface of female genital tract epithelial cells. This interaction allows such epithelial cells to efficiently transmit infective virus to susceptible targets and maintain viral infectivity for several days. Within the context of vaginal transmission, HIV must first traverse a normally protective mucosa containing a cell barrier to reach the underlying T cells and dendritic cells, which propagate and spread the infection. The mechanism by which HIV-1 can bypass an otherwise healthy cellular barrier remains an important area of study. Here, we demonstrate that genital tract-derived cell lines and primary human endocervical tissue can support direct transcytosis of cell-free virus from the apical to basolateral surfaces. Further, this transport of virus can be blocked through the addition of antibodies or peptides that directly block the interaction of gp340 with the HIV-1 envelope, if added prior to viral pulsing on the apical side of the cell or tissue barrier. Our data support a role for the previously described heparan sulfate moieties in mediating this transcytosis but add gp340 as an important facilitator of HIV-1 transcytosis across genital tract tissue. This study demonstrates that HIV-1 actively traverses the protective barriers of the human genital tract and presents a second mechanism whereby gp340 can promote heterosexual transmission.

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Section: Discussionmentioning

confidence: 85%

gp340 Promotes Transcytosis of Human Immunodeficiency Virus Type 1 in Genital Tract-Derived Cell Lines and Primary Endocervical Tissue

Stoddard

Cannon

et al. 2009

J Virol

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“…It has been shown that the majority of cells in clone C11 have characteristics of type b-intercalated cells, although the cells are not homogenous, as expected for a cloned cell line [16]. Moreover, it is known that bintercalated cells may differentiate to type a-intercalated cells in culture [17][18][19][20]. Therefore, to evaluate whether the expression of the a-subunit of Na + ,K + -ATPase in C11 cells is restricted to type a or type b intercalated cells, the cells were labeled for the asubunit of Na + ,K + -ATPase and PNA, a marker of bintercalated cells.…”

Section: Resultsmentioning

confidence: 96%

Lack of Na+,K+-ATPase expression in intercalated cells may be compensated by Na+-ATPase: A study on MDCK – C11 cells

Sampaio

Bezerra

Peçanha

et al. 2008

Cell. Mol. Life Sci.

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The lack of Na(+),K(+)-ATPase expression in intercalated cells (IC) is an intriguing condition due to its fundamental role in cellular homeostasis. In order to better understand this question we compared the activities of Na(+),K(+)-ATPase and Na(+)-ATPase in two MDCK cell clones: the C11, with IC characteristics, and the C7, with principal cells (PC) characteristics. The Na(+),K(+)-ATPase activity found in C11 cells is far lower than in C7 cells and the expression of its beta-subunit is similar in both cells. On the other hand, a subset of C11 without alpha-subunit expression has been found. In C11 cells the Na(+)-ATPase activity is higher than that of the Na(+),K(+)-ATPase, and it is increased by medium alkalinization, suggesting that it could account for the cellular Na(+)-homeostasis. Although further studies are necessary for a better understanding of these findings, the presence of Na(+)-ATPase may explain the adequate survival of cells that lack Na(+),K(+)-ATPase.

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“…We termed this protein hensin (9) (also termed DMBT1 by the Mouse Genome Project). We proposed that the conversion of intercalated cells is an example of terminal differentiation (10). Hensin/DMBT1 is expressed in most epithelia, often in alternately spliced forms, suggesting that hensin might be involved in the differentiation of other epithelia as well.…”

mentioning

confidence: 99%

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Gao

Eladari

Leviel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Acid–base transport in the renal collecting tubule is mediated by two canonical cell types: the β-intercalated cell secretes HCO 3 by an apical Cl:HCO 3 named pendrin and a basolateral vacuolar (V)-ATPase. Acid secretion is mediated by the α-intercalated cell, which has an apical V-ATPase and a basolateral Cl:HCO 3 exchanger (kAE1). We previously suggested that the β-cell converts to the α-cell in response to acid feeding, a process that depended on the secretion and deposition of an extracellular matrix protein termed hensin (DMBT1). Here, we show that deletion of hensin from intercalated cells results in the absence of typical α-intercalated cells and the consequent development of complete distal renal tubular acidosis (dRTA). Essentially all of the intercalated cells in the cortex of the mutant mice are canonical β-type cells, with apical pendrin and basolateral or diffuse/bipolar V-ATPase. In the medulla, however, a previously undescribed cell type has been uncovered, which resembles the cortical β-intercalated cell in ultrastructure, but does not express pendrin. Polymerization and deposition of hensin (in response to acidosis) requires the activation of β1 integrin, and deletion of this gene from the intercalated cell caused a phenotype that was identical to the deletion of hensin itself, supporting its critical role in hensin function. Because previous studies suggested that the conversion of β- to α-intercalated cells is a manifestation of terminal differentiation, the present results demonstrate that this differentiation proceeds from HCO 3 secreting to acid secreting phenotypes, a process that requires deposition of hensin in the ECM.

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Differentiation of columnar epithelia: the hensin pathway

Cited by 21 publications

References 26 publications

gp340 Promotes Transcytosis of Human Immunodeficiency Virus Type 1 in Genital Tract-Derived Cell Lines and Primary Endocervical Tissue

gp340 Promotes Transcytosis of Human Immunodeficiency Virus Type 1 in Genital Tract-Derived Cell Lines and Primary Endocervical Tissue

Lack of Na+,K+-ATPase expression in intercalated cells may be compensated by Na+-ATPase: A study on MDCK – C11 cells

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

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