| RRC ID |
63350
|
| 著者 |
Ohishi Y, Ammann S, Ziaee V, Strege K, Groß M, Amos CV, Shahrooei M, Ashournia P, Razaghian A, Griffiths GM, Ehl S, Fukuda M, Parvaneh N.
|
| タイトル |
Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement.
|
| ジャーナル |
Front Immunol
|
| Abstract |
Griscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused by RAB27A mutations that encode RAB27A, a member of the Rab GTPase family. RAB27A is expressed in many tissues and regulates vesicular transport and organelle dynamics. Occasionally, GS-2 patients with RAB27A mutation display normal pigmentation. The study of such variants provides the opportunity to map distinct binding sites for tissue-specific effectors on RAB27A. Here we present a new case of GS-2 without albinism (GS-2 sine albinism) caused by a novel missense mutation (Val143Ala) in the RAB27A and characterize its functional cellular consequences. Using pertinent animal cell lines, the Val143Ala mutation impairs both the RAB27A-SLP2-A interaction and RAB27A-MUNC13-4 interaction, but it does not affect the RAB27A-melanophilin (MLPH)/SLAC2-A interaction that is crucial for skin and hair pigmentation. We conclude that disruption of the RAB27A-MUNC13-4 interaction in cytotoxic lymphocytes leads to the HLH predisposition of the GS-2 patient with the Val143Ala mutation. Finally, we include a review of GS-2 sine albinism cases reported in the literature, summarizing their genetic and clinical characteristics.
|
| 巻・号 |
11
|
| ページ |
612977
|
| 公開日 |
2020-1-1
|
| DOI |
10.3389/fimmu.2020.612977
|
| PMID |
33362801
|
| PMC |
PMC7758216
|
| MeSH |
Adaptor Proteins, Signal Transducing / genetics
Adolescent
Albinism / genetics*
Animals
Binding Sites / genetics
COS Cells
Cell Line
Child
Child, Preschool
Chlorocebus aethiops
Female
Humans
Infant
Infant, Newborn
Leukocytes, Mononuclear / metabolism
Lymphohistiocytosis, Hemophagocytic / genetics*
Male
Membrane Proteins / genetics
Mutation, Missense / genetics
Piebaldism / genetics*
Primary Immunodeficiency Diseases / genetics*
rab GTP-Binding Proteins / genetics
rab27 GTP-Binding Proteins / genetics*
|
| IF |
5.085
|
| リソース情報 |
| 遺伝子材料 |
pMRX-bsr-EGFP-hRab27A (RDB18647)
pMRX-bsr-EGFP-hRab27A-V143A (RDB18648) |
