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Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement
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 vesicu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758216/ https://www.ncbi.nlm.nih.gov/pubmed/33362801 http://dx.doi.org/10.3389/fimmu.2020.612977 |
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author | Ohishi, Yuta Ammann, Sandra Ziaee, Vahid Strege, Katharina Groß, Miriam Amos, Carla Vazquez Shahrooei, Mohammad Ashournia, Parisa Razaghian, Anahita Griffiths, Gillian M. Ehl, Stephan Fukuda, Mitsunori Parvaneh, Nima |
author_facet | Ohishi, Yuta Ammann, Sandra Ziaee, Vahid Strege, Katharina Groß, Miriam Amos, Carla Vazquez Shahrooei, Mohammad Ashournia, Parisa Razaghian, Anahita Griffiths, Gillian M. Ehl, Stephan Fukuda, Mitsunori Parvaneh, Nima |
author_sort | Ohishi, Yuta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7758216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77582162020-12-25 Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement Ohishi, Yuta Ammann, Sandra Ziaee, Vahid Strege, Katharina Groß, Miriam Amos, Carla Vazquez Shahrooei, Mohammad Ashournia, Parisa Razaghian, Anahita Griffiths, Gillian M. Ehl, Stephan Fukuda, Mitsunori Parvaneh, Nima Front Immunol Immunology 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. Frontiers Media S.A. 2020-12-10 /pmc/articles/PMC7758216/ /pubmed/33362801 http://dx.doi.org/10.3389/fimmu.2020.612977 Text en Copyright © 2020 Ohishi, Ammann, Ziaee, Strege, Groß, Amos, Shahrooei, Ashournia, Razaghian, Griffiths, Ehl, Fukuda and Parvaneh http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ohishi, Yuta Ammann, Sandra Ziaee, Vahid Strege, Katharina Groß, Miriam Amos, Carla Vazquez Shahrooei, Mohammad Ashournia, Parisa Razaghian, Anahita Griffiths, Gillian M. Ehl, Stephan Fukuda, Mitsunori Parvaneh, Nima Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement |
title | Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement |
title_full | Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement |
title_fullStr | Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement |
title_full_unstemmed | Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement |
title_short | Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement |
title_sort | griscelli syndrome type 2 sine albinism: unraveling differential rab27a effector engagement |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758216/ https://www.ncbi.nlm.nih.gov/pubmed/33362801 http://dx.doi.org/10.3389/fimmu.2020.612977 |
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