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1 Departments of Medicine and Physiology and 2 Pediatrics, College of Physicians and Surgeons of Columbia University, New York, New York 10032
The band 3 anion
exchanger is located in the apical membrane of a 
-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 
-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.
kidney collecting duct; brain; CRP-ductin; ebnerin; epithelial polarity
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