| First Author | Kuliawat R | Year | 2009 |
| Journal | Eur J Cell Biol | Volume | 88 |
| Issue | 11 | Pages | 653-67 |
| PubMed ID | 19679373 | Mgi Jnum | J:157271 |
| Mgi Id | MGI:4430459 | Doi | 10.1016/j.ejcb.2009.07.001 |
| Citation | Kuliawat R, et al. (2009) A mutation within the transmembrane domain of melanosomal protein Silver (Pmel17) changes lumenal fragment interactions. Eur J Cell Biol 88(11):653-67 |
| abstractText | Melanocytes synthesize and store melanin within tissue-specific organelles, the melanosomes. Melanin deposition takes place along fibrils found within these organelles and fibril formation is known to depend on trafficking of the membrane glycoprotein Silver/Pmel17. However, correctly targeted, full-length Silver/Pmel17 cannot form fibers. Proteolytic processing in endosomal compartments and the generation of a lumenal Malpha fragment that is incorporated into amyloid-like structures is also essential. Dominant White (DWhite), a mutant form of Silver/Pmel17 first described in chicken, causes disorganized fibers and severe hypopigmentation due to melanocyte death. Surprisingly, the DWhite mutation is an insertion of three amino acids into the transmembrane domain; the DWhite-Malpha fragment is unaffected. To determine the functional importance of the transmembrane domain in organized fibril assembly, we investigated membrane trafficking and multimerization of Silver/Pmel17/DWhite proteins. We demonstrate that the DWhite mutation changes lipid interactions and disulfide bond-mediated associations of lumenal domains. Thus, partitioning into membrane microdomains and effects on conformation explain how the transmembrane region may contribute to the structural integrity of Silver/Pmel17 oligomers or influence toxic, amyloidogenic properties. |
