論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pMRX-bsr-EGFP-hRab27A (RDB18647) pMRX-bsr-EGFP-hRab27A-V143A (RDB18648) |