Integrin-alpha3 mediates binding of Chordin to the cell surface and promotes its endocytosis.
Dorsoventral patterning in animal development is regulated by a morphogenetic gradient of Bone morphogenetic protein signalling, which is established by a set of proteins that are conserved from Drosophila to vertebrates. These include Chordin (Chd)/Short gastrulation, Xolloid/Tolloid and Twisted gastrulation. Here, we report the identification of a cell-surface component of this morphogenetic pathway. Prompted by the observation that Chd protein bound to the surface of certain cell lines with subnanomolar affinity, we identified two cell-surface proteins that bind to Chd, one of which corresponds to Integrin-alpha3. Integrin-alpha3 and Chd are co-expressed in the Xenopus embryo. Transfection of Integrin-alpha3 increased the binding of Chd to the cell surface, which was competed by an excess of soluble Integrin-alpha3. After binding to the cell surface, Chd was translocated into intracellular endocytic compartments in a temperature-dependent manner. We propose that Integrin-alpha3 may regulate the concentration of Chd protein in the extracellular space by endocytosis.
Larraín
Juan
J
Howard Hughes Medical Institute, Department of Biological Chemistry, University of California, Los Angeles 90095-1662, USA.
Brown
Carlos
C
De Robertis
Eddy M
EM
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004330:Drosophila; D004705:Endocytosis; D006023:Glycoproteins / Q000378:metabolism*; D039422:Integrin alpha3 / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D011485:Protein Binding
D006023:Glycoproteins; D039422:Integrin alpha3; D036341:Intercellular Signaling Peptides and Proteins; C054234:chordin