The tetraspanin CD9 associates with the integrin alpha6beta4 in cultured human epidermal keratinocytes and is involved in cell motility.
Integrins are involved in several ways in keratinocyte physiology, including cell motility. CD9 is a member of the tetraspanin protein family which is found in association with other transmembrane proteins like the integrins. CD9 is expressed in the epidermal tissue, but this expression is not regulated by differentiation. The present work focuses on association of CD9 with the integrin alpha6beta4 in keratinocytes. In vivo, CD9 does not co-localize with alpha6beta4, and is not internalized with the integrin upon basal detachment with dispase. In vitro, CD9 is found partly in co-localization with alpha6beta4 and is internalized with the integrin after keratinocyte detachment with dispase. Using blocking antibodies in a phagokinetic tracks assay, we show that CD9, and to a lesser extent alpha6beta4, but not the tetraspanin CD82, promote motility of subconfluent keratinocytes on collagen I. Our observations also suggest that CD9 is involved in the formation of lamellipodia. We also report that the phorbol ester TPA has no effect on CD9 expression and association with alpha6beta4, but increases keratinocyte motility, possibly through modulation of integrin subunits expression, or through upregulation of collagenase-1 expression. Together, these results confirm that CD9 associates with alpha6beta4 in cultured keratinocytes, possibly in order to regulate the function of the integrin, and that CD9 is involved in keratinocyte motility on collagen. The data suggest that regulation of adhesion characteristics by CD9 in keratinocytes may play a role in epidermal repair.
Baudoux
B
B
Département Histologie-Embryologie, Facultés Universitaires Notre-Dame de la Paix, Namur/Belgium.
Castanares-Zapatero
D
D
Leclercq-Smekens
M
M
Berna
N
N
Poumay
Y
Y
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D000954:Antigens, Surface / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039161:Integrin alpha6beta4; D016023:Integrins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D011233:Precipitin Tests; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D060245:Tetraspanin 29
D015703:Antigens, CD; D000954:Antigens, Surface; C554869:CD9 protein, human; D039161:Integrin alpha6beta4; D016023:Integrins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D060245:Tetraspanin 29; D010450:Endopeptidases; C023139:dispase; D013755:Tetradecanoylphorbol Acetate