Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two forms of intercalated cells are present in kidney collecting tubules, the alpha cell has apical endocytosis, apical H+-ATPase and basolateral band 3, while beta cells have reversed polarity of these proteins and no apical endocytosis. When a beta cell line was seeded at high density, it changed into the alpha form. We previously showed that a partially purified 230 kD extracellular matrix protein of high density cells was able to retarget band 3 from apical to basolateral domains and stimulated apical endocytosis in vitro (Van Adelsberg, J., J.C. Edwards, J. Takito, B. Kiss, and Q. Al-Awqati. 1994. Cell. 76:1053-1061). We now purify this protein, which was named hensin, to near homogeneity and find that it belongs to the macrophage scavenger receptor cysteine rich (SRCR) family. An antibody, generated against a fusion protein made from a partial cDNA recognized a 230-kD protein in rabbit kidney and in the intercalated cell line. In vitro, the hensin antibody inhibited expression of apical endocytosis. Hensin was secreted in a polarized manner and bound to the basolateral membrane and extracellular matrix. Immunohistochemistry of the kidney showed that it was expressed only in collecting tubules. Double immunofluorescence with hensin and peanut lectin, H+-ATPase, or band 3 showed many patterns; most alpha-cells had hensin staining while 50% of beta-cells did not. These results suggest that hensin may also be involved in the polarity reversal of intercalated cells in vivo.
 ...
PMID:Hensin, a new collecting duct protein involved in the in vitro plasticity of intercalated cell polarity. 894 50

The collecting duct of the renal tubule contains two cell types, one of which, the intercalated cell, is responsible for acidification and alkalinization of urine. These cells exist in a multiplicity of morphological forms, with two extreme types, alpha and beta. The former acidifies the urine by an apical proton-translocating ATPase and a basolateral Cl/HCO3 exchanger, which is an alternately spliced form of band 3. This kidney form of band 3, kAE1, is present in the apical membrane of the beta-cell, which has the H+-ATPase on the basolateral membrane. We had suggested previously that metabolic acidosis leads to conversion of beta-types to alpha-types. To study the biochemical basis of this plasticity, we used an immortalized cell line of the beta-cell and showed that these cells convert to the alpha-phenotype when plated at superconfluent density. At high density these cells localize a new protein, which we term "hensin," to the extracellular matrix, and hensin acts as a molecular switch capable of changing the phenotype of these cells in vitro. Hensin induces new cytoskeletal proteins, makes the cells assume a more columnar shape and retargets kAE1 and the H+-ATPase. These recent studies suggest that the conversion of beta- to alpha-cells, at least in vitro, bears many of the hallmarks of terminal differentiation.
 ...
PMID:Phenotypic plasticity in the intercalated cell: the hensin pathway. 969 Oct 6

Intercalated epithelial cells exist in a spectrum of phenotypes; at one extreme, beta cells secrete HCO3 by an apical Cl/HCO3 exchanger and a basolateral H+ ATPase. When an immortalized beta cell line is seeded at high density it deposits in its extracellular matrix (ECM) a new protein, hensin, which can reverse the polarity of several proteins including the Cl/HCO3 exchanger (an alternately spliced form of band 3) and the proton translocating ATPase. When seeded at low density and allowed to form monolayers these polarized epithelial cells maintain the original distribution of these two proteins. Although these cells synthesize and secrete hensin, it is not retained in the ECM, but rather, hensin is present in a large number of intracellular vesicles. The apical cytoplasm of low density cells is devoid of actin, villin, and cytokeratin19. Scanning electron microscopy shows that these cells have sparse microvilli, whereas high density cells have exuberant apical surface infolding and microvilli. The apical cytoplasm of high density cells contains high levels of actin, cytokeratin19, and villin. The cell shape of these two phenotypes is different with high density cells being tall with a small cross-sectional area, whereas low density cells are low and flat. This columnarization and the remodeling of the apical cytoplasm is hensin-dependent; it can be induced by seeding low density cells on filters conditioned by high density cells and prevented by an antibody to hensin. The changes in cell shape and apical cytoskeleton are reminiscent of the processes that occur in terminal differentiation of the intestine and other epithelia. Hensin is highly expressed in the intestine and prostate (two organs where there is a continuous process of differentiation). The expression of hensin in the less differentiated crypt cells of the intestine and the basal cells of the prostate is similar to that of low density cells; i.e., abundant intracellular vesicles but no localization in the ECM. On the other hand, as in high density cells hensin is located exclusively in the ECM of the terminally differentiated absorptive villus cells and the prostatic luminal cell. These studies suggest that hensin is a critical new molecule in the terminal differentiation of intercalated cell and perhaps other epithelial cells.
 ...
PMID:Hensin remodels the apical cytoskeleton and induces columnarization of intercalated epithelial cells: processes that resemble terminal differentiation. 1008 1

The band 3 anion exchanger is located in the apical membrane of a beta-intercalated clonal cell line, whereas the vacuolar H(+)-ATPase is present in the basolateral membrane. When these cells were seeded at confluent density, they converted to an alpha-phenotype, localizing each of these proteins to the opposite cell membrane domain. The reversal of polarity is induced by hensin, a 230-kDa extracellular matrix protein. Rabbit kidney hensin is a multidomain protein composed of eight SRCR ("scavenger receptor, cysteine rich"), two CUB ("C1r/C1s Uegf Bmp1"), and one ZP ("zona pellucida") domain. Other proteins known to have these domains include CRP-ductin, a cDNA expressed at high levels in mouse intestine (8 SRCR, 5 CUB, 1 ZP), ebnerin, a protein cloned from a rat taste bud library (4 SRCR, 3 CUB, 1 ZP), and DMBT1, a sequence in human chromosome 10q25-26 frequently deleted in malignant gliomas (9 SRCR, 2 CUB, 1 ZP). Rabbit and mouse hensin genomic clones contained a new SRCR that was not found in hensin cDNA but was homologous to the first SRCR domain in DMBT1. Furthermore, the 3'-untranslated regions and the signal peptide of hensin were homologous to those of DMBT1. Mouse genomic hensin was localized to chromosome 7 band F4, which is syntenic to human 10q25-26. These data suggest that hensin and DMBT1 are alternatively spliced forms of the same gene. The analysis of mouse hensin bacterial artificial chromosome (BAC) genomic clone by sequencing and Southern hybridization revealed that the gene also likely encodes CRP-ductin. A new antibody against the mouse SRCR1 domain recognized a protein in the mouse and rabbit brain but not in the immortalized cell line or kidney, whereas an antibody to SRCR6 and SRCR7 domains which are present in all the transcripts, recognized proteins in intestine, kidney, and brain from several species. The most likely interpretation of these data is that one gene produces at least three transcripts, namely, hensin, DMBT1, and CRP-ductin. Hensin may participate in determining the polarized phenotype of other epithelia and brain cells.
 ...
PMID:Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas. 1044 83

The intercalated cell of the collecting tubule exists in a spectrum of types. The alpha form secretes acid by an apical H+-ATPase and a basolateral CI:HCO3 exchanger, which is an alternatively spliced form of the red cell band 3 (kAE1), and the beta form secretes HCO3 by having these transporters on the reverse membranes. In a clonal cell line of the beta form, we found that seeding density causes conversion of beta cells to the alpha form. A new protein, termed hensin, was deposited in the extracellular matrix (ECM) of high-density cells, which, on purification, reversed the polarity of the transporters. Hensin also induced the expression of the microvillar protein villin and caused the appearance of the apical terminal web proteins, cytokeratin 19 and actin; all of which led to the development of an exuberant microvillar structure. In addition, hensin caused the beta cells to assume a columnar shape. All of these studies show that the conversion of polarity in the intercalated cell, at least in vitro, represents terminal differentiation and that hensin is the first protein in a new pathway that mediates this process. Hensin, DMBT1, CRP-ductin, and ebnerin are alternately spliced products from a single gene located in human chromosome 10q25-26, a region often deleted in several cancers, especially malignant gliomas. Hensin is expressed in many epithelial cell types and it is possible that it plays a similarly important role in the differentiation of these epithelia as well.
 ...
PMID:Terminal differentiation in epithelia: the Hensin pathway in intercalated cells. 1051 81

The intercalated cell of the collecting tubule exists in a spectrum of types. The alpha form secretes acid by an apical H(+) ATPase and a basolateral Cl:HCO(3) exchanger which is an alternatively spliced form of the red cell band 3 (kAE1), while the beta form secretes HCO(3) by having these transporters on the reverse membranes. In a clonal cell line of the beta form we found that seeding density causes this conversion. A new protein, termed hensin, was deposited in the extracellular matrix of high-density cells which on purification reversed the polarity of the transporters. Hensin also induced the expression of the microvillar protein, villin, and caused the appearance of the apical terminal web proteins, cytokeratin 19 and actin, all of which led to the development of an exuberant microvillar structure. In addition, hensin caused the beta cells to assume a columnar shape. All of these studies demonstrate that the conversion of polarity in the intercalated cell, at least in vitro, represents terminal differentiation and that hensin is the first protein in a new pathway that mediates this process. Hensin, DMBT1, CRP-ductin, and ebnerin are alternately spliced products from a single gene located on human chromosome 10q25-26, a region often deleted in several cancers, especially malignant gliomas. Hensin is expressed in many epithelial cell types, and it is possible that it plays a similarly important role in the differentiation of these epithelia as well.
 ...
PMID:Phenotypic plasticity and terminal differentiation of the intercalated cell: the hensin pathway. 1072 44