Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas

Abstract

The band 3 anion exchanger is located in the apical membrane of a β-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 α-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.

Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

“…The DMBT1 gene encodes orthologs in rabbit (hensin (Takito et al 1999)), mouse (CRP-ductin (Cheng et al 1996, Madsen et al 2003 and vomeroglandin (Matsushita et al 2000)), rat (ebnerin (Li & Snyder 1995)), bovine (bovine gallbladder mucin (Nunes et al 1995, Mollenhauer et al 2001), human (gp-340 in lung (Holmskov et al 1997 and salivary agglutinin in saliva (Prakobphol et al 2000, Ligtenberg et al 2001), and porcine (sperm binding glycoprotein (SBG; Teijeiro et al 2012)) species. The pig SBG has been shown to be present in the oviduct, at the apical surface of isthmic and ampullar epithelial cells (Perez et al 2006), to bind to the heads of pig sperm (Marini & Cabada 2003) and to be involved in sperm selection in the oviduct (Teijeiro et al 2008).…”

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

“…Each group of investigators has given the gene/protein different names, and there are many proposed functions. The different names include Muclin (12), gp340 (31), salivary agglutinin (16,42), crp-ductin (6), ebnerin (29), hensin (54), vomeroglandin (33), and DMBT1 (37). We coined the name Muclin (mucin-like glycoprotein), which is based on the glycoprotein's biochemical characteristics (8).…”

2007 Homer W. Smith Award

“…When a clonal cell line was seeded at low density on a hensincontaining ECM, they developed apical endocytosis and apical microvilli, demonstrating again that the density of seeding was not actually a "contact inhibition" type of phenomenon. 24,25 Apical microvilli require the presence of elaborate cytoskeleton, and indeed we found that high-density cells induce the production of villin and cytokeratin 19, proteins that are absent in low-density cells. All of these phenomena were induced by hensin purified to homogeneity.…”