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AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

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AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking. / Setta-Kaffetzi, Niovi; Simpson, Michael A; Navarini, Alexander A; Patel, Varsha M; Lu, Hui-Chun; Allen, Michael H; Duckworth, Michael; Bachelez, Hervé; Burden, A David; Choon, Siew-Eng; Griffiths, Christopher E M; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M B; Prins, Christa; Smahi, Asma; Trembath, Richard C; Fraternali, Franca; Smith, Catherine H; Barker, Jonathan N; Capon, Francesca.

In: American Journal of Human Genetics, Vol. 94, No. 5, 05.2014, p. 790-797.

Research output: Contribution to journalArticle

Harvard

Setta-Kaffetzi, N, Simpson, MA, Navarini, AA, Patel, VM, Lu, H-C, Allen, MH, Duckworth, M, Bachelez, H, Burden, AD, Choon, S-E, Griffiths, CEM, Kirby, B, Kolios, A, Seyger, MMB, Prins, C, Smahi, A, Trembath, RC, Fraternali, F, Smith, CH, Barker, JN & Capon, F 2014, 'AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking', American Journal of Human Genetics, vol. 94, no. 5, pp. 790-797. https://doi.org/10.1016/j.ajhg.2014.04.005

APA

Setta-Kaffetzi, N., Simpson, M. A., Navarini, A. A., Patel, V. M., Lu, H-C., Allen, M. H., Duckworth, M., Bachelez, H., Burden, A. D., Choon, S-E., Griffiths, C. E. M., Kirby, B., Kolios, A., Seyger, M. M. B., Prins, C., Smahi, A., Trembath, R. C., Fraternali, F., Smith, C. H., ... Capon, F. (2014). AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking. American Journal of Human Genetics, 94(5), 790-797. https://doi.org/10.1016/j.ajhg.2014.04.005

Vancouver

Setta-Kaffetzi N, Simpson MA, Navarini AA, Patel VM, Lu H-C, Allen MH et al. AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking. American Journal of Human Genetics. 2014 May;94(5):790-797. https://doi.org/10.1016/j.ajhg.2014.04.005

Author

Setta-Kaffetzi, Niovi ; Simpson, Michael A ; Navarini, Alexander A ; Patel, Varsha M ; Lu, Hui-Chun ; Allen, Michael H ; Duckworth, Michael ; Bachelez, Hervé ; Burden, A David ; Choon, Siew-Eng ; Griffiths, Christopher E M ; Kirby, Brian ; Kolios, Antonios ; Seyger, Marieke M B ; Prins, Christa ; Smahi, Asma ; Trembath, Richard C ; Fraternali, Franca ; Smith, Catherine H ; Barker, Jonathan N ; Capon, Francesca. / AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking. In: American Journal of Human Genetics. 2014 ; Vol. 94, No. 5. pp. 790-797.

Bibtex Download

@article{1c434bfb02944eec9a808a7cc37a48ed,
title = "AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking",
abstract = "Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.",
author = "Niovi Setta-Kaffetzi and Simpson, {Michael A} and Navarini, {Alexander A} and Patel, {Varsha M} and Hui-Chun Lu and Allen, {Michael H} and Michael Duckworth and Herv{\'e} Bachelez and Burden, {A David} and Siew-Eng Choon and Griffiths, {Christopher E M} and Brian Kirby and Antonios Kolios and Seyger, {Marieke M B} and Christa Prins and Asma Smahi and Trembath, {Richard C} and Franca Fraternali and Smith, {Catherine H} and Barker, {Jonathan N} and Francesca Capon",
year = "2014",
month = may,
doi = "10.1016/j.ajhg.2014.04.005",
language = "English",
volume = "94",
pages = "790--797",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Elsevier",
number = "5",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

AU - Setta-Kaffetzi, Niovi

AU - Simpson, Michael A

AU - Navarini, Alexander A

AU - Patel, Varsha M

AU - Lu, Hui-Chun

AU - Allen, Michael H

AU - Duckworth, Michael

AU - Bachelez, Hervé

AU - Burden, A David

AU - Choon, Siew-Eng

AU - Griffiths, Christopher E M

AU - Kirby, Brian

AU - Kolios, Antonios

AU - Seyger, Marieke M B

AU - Prins, Christa

AU - Smahi, Asma

AU - Trembath, Richard C

AU - Fraternali, Franca

AU - Smith, Catherine H

AU - Barker, Jonathan N

AU - Capon, Francesca

PY - 2014/5

Y1 - 2014/5

N2 - Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.

AB - Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.

U2 - 10.1016/j.ajhg.2014.04.005

DO - 10.1016/j.ajhg.2014.04.005

M3 - Article

C2 - 24791904

VL - 94

SP - 790

EP - 797

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -

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