TABLE 1:
Summary of the phenotypes of PMEL deletion and alanine-scanning mutants.
| Mutant | Description | Category |
|---|---|---|
| NTR50 | Δ28-50 | Formation of normal melanosomes (indistinguishable from wt-PMEL) |
| NTR63 | Δ51-63 | Formation of normal melanosomes (indistinguishable from wt-PMEL) |
| NTR123 | Δ99-123 | Formation of normal melanosomes (indistinguishable from wt-PMEL) |
| NTR97 | Δ91-97 | Fibril deposition in both normal melanosomes and lysosomal organelles |
| NTR137 | Δ124-137 | Fibril deposition in both normal melanosomes and lysosomal organelles |
| ALA66 | 64GQV66→AAA | Fibril deposition only in lysosomal organelles |
| ALA69T | 67SLK69→AAA | Fibril deposition in both normal melanosomes and lysosomal organelles |
| ALA87 | 85SIA87→AAG | Fibril deposition in both normal melanosomes and lysosomal organelles |
| ALA142 | 138CPSGS142→AAAAA | Fibril deposition in both normal melanosomes and lysosomal organelles |
| ALA147 | 143WSQKR147→AAAAA | Fibril deposition in both normal melanosomes and lysosomal organelles |
| ALA166 | 163LGGP166→AAAA | Not analyzed by EM, but IF shows all mature protein in LAMP1high lysosomes |
| ALA72 | 70VSN72→AAA | Golgi retention/no fibril formation |
| ALA78 | 76TLI78→AAA | Golgi retention/no fibril formation |
| ALA81 | 79GAN81→AGA | Golgi retention/no fibril formation |
| ALA177 | 172IGTGRA177→AAAAAG | Golgi retention/no fibril formation |
| ALA75 | 73DGP75→AAA | Golgi and early endosomal distribution/no fibril formation |
| ALA157 | 153WKTWG157→AAAAA | Golgi and early endosomal distribution/no fibril formation |
| ALA162 | 158QYWQV162→AAAAA | Golgi and early endosomal distribution/no fibril formation |
| ALA198 | 194SRSYV198→AAAAA | Golgi and early endosomal distribution/no fibril formation |
| NTR75 | Δ51-75 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR98 | Δ76-98 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR166 | Δ124-166 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR199 | Δ167-199 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR74 | Δ64-74 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR90 | Δ75-90 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR156 | Δ138-156 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| NTR165 | Δ157-165 | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA84 | 82ASF84→GAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA90T | 88LNF90→AAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA152 | 148SFVYV152→AAAAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA171 | 167VSGLS171→AAAAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA183 | 178MLGTHT183→AAAAAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA188 | 184MEVTV188→AAAAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
| ALA193 | 189YHRRG193→AAAAA | Complete ER retention/minimal reactivity with conformation-sensitive antibody HMB50 |
The phenotypes of the PMEL deletion and alanine-scanning mutants (Figure 2, A and B) generated in this study fell into the five indicated categories. Figure 2C maps the respective phenotypes onto a pictogram of the NTR. The color code corresponds to the color code used in Figure 2C.