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Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2625-2626
CORRESPONDENCE
AC133 Hematopoietic Stem Cell Antigen: Human Homologue of Mouse
Kidney Prominin or Distinct Member of a Novel Protein Family?
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LETTER |
To the Editor:
In the December 15, 1997 issue of BLOOD, Miraglia et al1
reported the sequence of the AC133 antigen, a novel 865 amino acid-residue surface glycoprotein found in human hematopoietic stem
and progenitor cells. In the November 11, 1997 issue of Proceedings of the National Academy of Sciences of the United States of
America, our group2 described the novel protein
prominin, an 858 amino acid-residue polytopic membrane protein
specific to microvilli on the apical surface of various murine
embryonic and adult epithelia. We wish to bring to the attention of the
readers of BLOOD that the human AC133 antigen and mouse prominin are
highly related proteins that share the same 5-transmembrane topology
and show an average 60% amino acid-sequence identity (Fig
1) and to discuss implications of this
relationship.
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| Fig 1.
Sequence alignment of the mouse prominin (mPRO), human
AC133 (hAC133), and C elegans open reading frame F08B12.1.
Boxes indicate identical amino acid residues in corresponding sequence
positions. Red, hydrophobic; blue, hydrophilic.
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First, the AC133 antigen may be the human homologue of mouse prominin.
This would imply that (1) there is considerable species variation
between human and murine prominin/AC133 antigen, in particular in the
extracellular domains and (2) the cellular distribution of
prominin/AC133 antigen is broader than assumed from the results of the
two initial studies.1-3 Evidence consistent with this possibility includes the following points. The monoclonal antibody 13A4
used to isolate the prominin cDNA clone from adult mouse kidney
recognizes a similar, if not identical, protein in the neuroepithelium
of mouse embryos, and EST sequences from human retina, which originates
from the neuroepithelium, are more closely related to the human AC133
sequence than to that of mouse kidney prominin. Also, AC133
immunoreactivity is detected in the human NT2 cell line,3
which exhibits neuroepithelial features. If the AC133 antigen is the
human homologue of mouse prominin, the lack of AC133 immunoreactivity
in human kidney may reflect the fact that the monoclonal antibody AC133
recognizes a glycosylated structure,1 which would imply
differential glycosylation of prominin/AC133 antigen in various cell
types.
Second, prominin and the AC133 antigen may be distinct members of a
novel family of membrane proteins. If so, the difference between
epithelial and nonepithelial members of this protein family may account
for some, if not most, of the sequence variation between mouse kidney
prominin and the human hematopoietic stem cell antigen AC133. Evidence
consistent with the existence of multiple members of the prominin/AC133
antigen family within a given species includes the following examples.
Northern blot analysis using the mouse kidney prominin cDNA as probe
reveals the presence of similar RNAs in mouse kidney and gut, whereas
immunoreactivity is detected in kidney, but not gut, using either the
13A4 monoclonal antibody2 or two polyclonal antibodies
raised against recombinant mouse kidney prominin (D. Corbeil,
unpublished data). Likewise, AC133 transcripts were
detected in various human tissues whereas AC133 immunoreactivity was
confined to human bone marrow.1 Interestingly, the
Caenorhabditis elegans genome4
contains, in addition to the predicted protein F08B12.1
that is strikingly similar to mouse prominin2 and the human
AC133 antigen (Fig 1), at least two other open reading frames
(M28.9 and M28.8, accession no. Z49911) that predict proteins
related in size and hydropathy pattern to mouse prominin and the
human AC133 antigen.
It will be important to determine whether a key feature of prominin,
its selective targetting to plasma membrane protrusions, is also
observed for the AC133 antigen in hematopoietic stem cells. If so, and
on the assumption that for any given species there will be more than
one prominin/AC133 protein, the prominin of epithelial cells could be
referred to as E-prominin and the AC133 antigen perhaps as H-prominin
(for hematopoietic stem cell prominin).
Even more importantly, the function of prominin/AC133 proteins remains
to be established. One may speculate whether the expression of prominin
in various murine embryonic epithelia and of the AC133 antigen in human
hematopoietic stem cells provides a clue for a role of these novel
membrane proteins in cell determination.
Denis Corbeil
Katja Röper
Anja Weigmann
Wieland B. Huttner
Department of Neurobiology
University of
Heidelberg
Heidelberg, Germany
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REFERENCES |
1.
Miraglia S,
Godfrey W,
Yin AH,
Atkins K,
Warnke R,
Holden JT,
Bray RA,
Waller EK,
Buck DW:
A novel five-transmembrane hematopoietic stem cell antigen: Isolation, characterization, and molecular cloning.
Blood
90:5013,
1997[Abstract/Free Full Text]
2.
Weigmann A,
Corbeil D,
Hellwig A,
Huttner WB:
Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells.
Proc Natl Acad Sci USA
94:12425,
1997[Abstract/Free Full Text]
3.
Yin AH,
Miraglia S,
Zanjani ED,
Almeida-Porada G,
Ogawa M,
Leary AG,
Olweus J,
Kearney J,
Buck DW:
AC133, a novel marker for human hematopoietic stem and progenitor cells.
Blood
90:5002,
1997[Abstract/Free Full Text]
4.
Wilson R,
:
2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans.
Nature
368:32,
1994[Medline]
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