A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface.
In general, plasma membrane integral proteins, such as the membrane-anchored growth factor proTGF-alpha, are assumed to be transported to the cell surface via a nonregulated, constitutive pathway. proTGF-alpha C-terminal mutants are retained in an early secretory compartment. Here, using a two-hybrid screen, we identify two TACIPs (proTGF-alpha cytoplasmic domain-interacting proteins) that contain PDZ domains and do not interact with proTGF-alpha C-terminal mutants. The binding specificity of one of them, TACIP18 (previously identified and named Syntenin or mda-9), coincides with that of the component that possibly mediates the normal trafficking of proTGF-alpha. TACIP18 colocalizes and interacts specifically with immature, intracellular forms of proTGF-alpha. Therefore, it appears that the interaction of TACIP18 with proTGF-alpha in the early secretory pathway is necessary for the targeting of the latter to the cell surface.
Fernández-Larrea
J
J
Laboratori de Recerca Oncològica, Hospital General Universitari Vall d'Hebron, Barcelona, Spain.
Merlos-Suárez
A
A
Ureña
J M
JM
Baselga
J
J
Arribas
J
J
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism; D006224:Cricetinae; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000737:chemistry; D011509:Proteoglycans / Q000378:metabolism; D053669:Syndecan-2; D053676:Syntenins; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011509:Proteoglycans; C508245:SDC2 protein, human; C109621:SDCBP protein, human; D053676:Syntenins; D016211:Transforming Growth Factor alpha; C052268:protransforming growth factor alpha; C091825:syntrophin alpha1; D053669:Syndecan-2