Integrity of all four transmembrane domains of the tetraspanin uroplakin Ib is required for its exit from the ER

Abstract

SummaryIntegrity of all four transmembrane domains of the tetraspanin uroplakin Ib is required for its exit from the ER

Transmembrane Interactions Are Needed for KAI1/CD82-Mediated Suppression of Cancer Invasion and Metastasis

“…Although the precise role of these polar residues in tetraspanin function remains unknown, recent studies suggest that the strong polar residues in CD9, CD81, and UPIb are involved in molecular packing, ie, the interactions between TM segments. [13][14][15] This notion agrees with earlier observations made from other TM proteins that TM polar residues can mediate peptide-peptide interactions within the lipid bilayer. 16 -20 Furthermore, studies from T cell receptor demonstrated that the TM polar residues contribute to the assembly, cell surface expression, and signaling of T cell receptor, [21][22][23] underscoring the biological significance of TM polar residues.…”

“…2 also found in tetraspanin UPIb, in which a mutation of the Glu residue in the third TM domain causes the ER retention of UPIb. 15 We found in this study that the Asn 17 residue in the first TM region of CD82 unlikely plays a role of CD82's first TM region in the ER exit. In addition, the Asn 17 residue appears not to be needed for the dimerization of CD82, although the corresponding polar residue in the CD9 TM1 helix is involved in the homodimerization of CD9.…”

“…Moreover, once the interactions between the TM domains are disrupted, tetraspanins form protein aggregates intracellularly likely as a result of destabilized or misfolded conformation. 15,33 The NQE mutant did not form aggregates inside cells and expressed equally at the cell surface as the wild-type, further suggesting that the global structure of CD82 remains intact. However, the conformation of CD82 becomes less stable.…”

“…A mutation of the Asn (N) residue in the TM1 domain of tetraspanin CD9 results in less homodimerization of CD9, 13 while the biochemical roles of the other two TM polar residues in CD9 remain to be determined. A Glu 3 Ala mutation in the TM3 domain of tetraspanin UPIb causes its endoplasmic reticulum (ER) retention, 15 probably because of the misfolding of the proteins. However, the roles of TM polar residues in biological functions of CD9 and UPIb remain unknown.…”

Association of tetraspanin CD9 with transmembrane TGFα confers alterations in cell-surface presentation of TGFα and cytoskeletal organization

“…The tetraspanin CD81 facilitates the processing and transport of the glycoprotein CD19, starting with its requirement for exit from the endoplasmic reticulum to the processing and glycosylation of CD19 (Shoham et al, 2006). The tetraspanins uroplakin Ia and uroplakin Ib allow transit of the nontetraspanin uroplakins UPII and UPIII from the Golgi to the cell surface to form urothelial plaques (Tu et al, 2006). We now provide evidence for a role of CD9 in processing and cell-surface presentation of TGFα, suggesting similar effects on all TGFα-family proteins.…”