Cell surface counter receptors are essential components of the unconventional export machinery of galectin-1.
Galectin-1 is a component of the extracellular matrix as well as a ligand of cell surface counter receptors such as beta-galactoside-containing glycolipids, however, the molecular mechanism of galectin-1 secretion has remained elusive. Based on a nonbiased screen for galectin-1 export mutants we have identified 26 single amino acid changes that cause a defect of both export and binding to counter receptors. When wild-type galectin-1 was analyzed in CHO clone 13 cells, a mutant cell line incapable of expressing functional galectin-1 counter receptors, secretion was blocked. Intriguingly, we also find that a distant relative of galectin-1, the fungal lectin CGL-2, is a substrate for nonclassical export from Chinese hamster ovary (CHO) cells. Alike mammalian galectin-1, a CGL-2 mutant defective in beta-galactoside binding, does not get exported from CHO cells. We conclude that the beta-galactoside binding site represents the primary targeting motif of galectins defining a galectin export machinery that makes use of beta-galactoside-containing surface molecules as export receptors for intracellular galectin-1.
Seelenmeyer
Claudia
C
Heidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany.
Wegehingel
Sabine
S
Tews
Ivo
I
Künzler
Markus
M
Aebi
Markus
M
Nickel
Walter
W
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005656:Fungal Proteins / Q000378:metabolism; D005697:Galactosides / Q000737:chemistry / Q000378:metabolism; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D037501:Galectin 2; D037161:Galectins / Q000378:metabolism; D005786:Gene Expression Regulation; D006017:Glycolipids / Q000037:antagonists & inhibitors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008024:Ligands; D009154:Mutation; D021381:Protein Transport / Q000502:physiology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*
C103751:CGL2 protein, Coprinus cinereus; D005656:Fungal Proteins; D005697:Galactosides; D037483:Galectin 1; D037501:Galectin 2; D037161:Galectins; D006017:Glycolipids; D008024:Ligands; D011956:Receptors, Cell Surface; C007816:beta-galactoside; D049452:Green Fluorescent Proteins