Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter.
Cell fusion involving progenitor cells is a newly recognized phenomenon thought to contribute to tissue differentiation. The molecular mechanisms governing cell fusion are unknown. P-glycoprotein and related ATP-binding cassette transporters are expressed by progenitor cells, but their physiological role in these cell types has not been defined. Here, we have cloned ABCB5, a rhodamine efflux transporter and novel member of the human P-glycoprotein family, which marks CD133-expressing progenitor cells among human epidermal melanocytes and determines as a regulator of membrane potential the propensity of this subpopulation to undergo cell fusion. Our findings show that polyploid ABCB5+ cells are generated by cell fusion and that this process is specifically enhanced by ABCB5 P-glycoprotein blockade. Remarkably, multinucleated cell hybrids gave rise to mononucleated progeny, demonstrating that fusion contributes to culture growth and differentiation. Thus, our findings define a molecular mechanism for cell fusion involving progenitor cells and show that fusion and resultant growth and differentiation are not merely spontaneous events, but phenomena regulated by ABCB5 P-glycoprotein.
Frank
Natasha Y
NY
Partners Center for Human Genetics, Harvard Medical School, Boston, MA 02115, USA. mfrank@rics.bwh.harvard.edu
Pendse
Shona S
SS
Lapchak
Peter H
PH
Margaryan
Armen
A
Shlain
Debbie
D
Doeing
Carsten
C
Sayegh
Mohamed H
MH
Frank
Markus H
MH
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000502:physiology*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011123:Polyploidy; D012867:Skin / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection
C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters