| RRC ID |
49212
|
| Author |
Ohbayashi N, Mamishi S, Ishibashi K, Maruta Y, Pourakbari B, Tamizifar B, Mohammadpour M, Fukuda M, Parvaneh N.
|
| Title |
Functional characterization of two RAB27A missense mutations found in Griscelli syndrome type 2.
|
| Journal |
Pigment Cell Melanoma Res
|
| Abstract |
Human Griscelli syndrome type 2 (GS-2) is characterized by partial albinism and a severe immunologic disorder as a result of RAB27A mutations. In melanocytes, Rab27A forms a tripartite complex with a specific effector Slac2-a/melanophilin and myosin Va, and the complex regulates melanosome transport. Here, we report a novel homozygous missense mutation of Rab27A, i.e. K22R, in a Persian GS-2 patient and the results of analysis of the impact of the K22R mutation and the previously reported I44T mutation on protein function. Both mutations completely abolish Slac2-a/melanophilin binding activity but they affect the biochemical properties of Rab27A differently. The Rab27A(K22R) mutant lacks the GTP binding ability and exhibits cytosolic localization in melanocytes. By contrast, neither intrinsic GTPase activity nor melanosomal localization of Rab27A is affected by the I44T mutation, but the Rab27A(I44T) mutant is unable to recruit Slac2-a/melanophilin. Interestingly, the two mutations differently affect binding to other Rab27A effectors, Slp2-a, Slp4-a/granuphilin-a, and Munc13-4. The Rab27A(K22R) mutant normally binds Munc13-4, but not Slp2-a or Slp4-a, whereas the Rab27A(I44T) mutant shows reduced binding activity to Slp2-a and Munc13-4 but normally binds Slp4-a.
|
| Volume |
23(3)
|
| Pages |
365-74
|
| Published |
2010-6-1
|
| DOI |
10.1111/j.1755-148X.2010.00705.x
|
| PII |
PCR705
|
| PMID |
20370853
|
| MeSH |
Adaptor Proteins, Signal Transducing / metabolism
Guanosine Triphosphate / metabolism
Humans
Immunologic Deficiency Syndromes / genetics*
Immunologic Deficiency Syndromes / pathology
Melanosomes / metabolism
Mutant Proteins / metabolism
Mutation, Missense / genetics*
Phenotype
Protein Binding
Protein Transport
Subcellular Fractions / metabolism
rab GTP-Binding Proteins / genetics*
rab27 GTP-Binding Proteins
|
| IF |
3.683
|
| Times Cited |
11
|
|
WOS Category
|
DERMATOLOGY
ONCOLOGY
CELL BIOLOGY
|
| Resource |
| DNA material |
pEF-mouse T7-Munc13-4 (RDB15181) |
