Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma
Nature Genetics, Volume 44, No. 11, Year 2012
Notification
URL copied to clipboard!
Description
Palmoplantar keratodermas (PPKs) are a group of disorders that are diagnostically and therapeutically problematic in dermatogenetics. Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on the palms and soles with considerable heterogeneity. In 18 families with autosomal dominant punctate PPK, we report heterozygous loss-of-function mutations in AAGAB, encoding α-and γ-adaptin-binding protein p34, located at a previously linked locus at 15q22. α-and γ-adaptin-binding protein p34, a cytosolic protein with a Rab-like GTPase domain, was shown to bind both clathrin adaptor protein complexes, indicating a role in membrane trafficking. Ultrastructurally, lesional epidermis showed abnormalities in intracellular vesicle biology. Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of AAGAB in keratinocytes led to increased cell division, which was linked to greatly elevated epidermal growth factor receptor (EGFR) protein expression and tyrosine phosphorylation. We hypothesize that p34 deficiency may impair endocytic recycling of growth factor receptors such as EGFR, leading to increased signaling and cellular proliferation. © 2012 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Pohler, Elizabeth
United Kingdom, Dundee
University of Dundee
Mamaï, Ons
Tunisia, Sousse
Hopital Farhat Hached Sousse
Singapore, Singapore City
A-star, Institute of Medical Biology
Hirst, Jennifer
United Kingdom, Cambridge
Cambridge Institute for Medical Research
Zamiri, Mozheh
United Kingdom, Crosshouse
University Hospital Crosshouse
Horn, Helen
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Nomura, Toshifumi
Japan, Sapporo
Graduate School of Medicine
Irvine, Alan D.
Ireland, Dublin
Our Lady's Hospital for Sick Children
Ireland, Dublin
Trinity College Dublin
Moran, Benvon
Ireland, Dublin
Our Lady's Hospital for Sick Children
Wilson, Neil J.
United Kingdom, Dundee
University of Dundee
Smith, Frances J.D.
United Kingdom, Dundee
University of Dundee
Goh, Christabelle S.M.
United Kingdom, Dundee
University of Dundee
Sandilands, Aileen
United Kingdom, Dundee
University of Dundee
Cole, Christian
United Kingdom, Dundee
University of Dundee
Barton, Geoffrey J.
United Kingdom, Dundee
University of Dundee
Evans, Alan T.
United Kingdom, Dundee
University of Dundee School of Medicine
Shimizu, Hiroshi
Japan, Sapporo
Graduate School of Medicine
Akiyama, Masashi
Japan, Nagoya
Nagoya University Graduate School of Medicine
Suehiro, Mitsuhiro
Japan, Otsu
Otsu Municipal Hospital
Konohana, Izumi
Japan, Hiratsuka
Hiratsuka Municipal Hospital
Al-Shboul, Mohammad
Singapore, Singapore City
A-star, Institute of Medical Biology
Teissier, Sebastien
Singapore, Singapore City
A-star, Institute of Medical Biology
Boussofara, Lobna
Tunisia, Sousse
Hopital Farhat Hached Sousse
Denguezli, Mohamed
Tunisia, Sousse
Hopital Farhat Hached Sousse
Saâd, Ali
Tunisia, Sousse
Hopital Farhat Hached Sousse
Gribaa, Moez
Tunisia, Sousse
Hopital Farhat Hached Sousse
Dopping-Hepenstal, Patricia J.C.
United Kingdom, London
St Thomas' Hospital
McGrath, J. A.
United Kingdom, London
King's College London
Brown, S. J.
United Kingdom, Dundee
University of Dundee
Goudie, David R.
United Kingdom, Dundee
University of Dundee School of Medicine
Reversade, Bruno
Singapore, Singapore City
A-star, Institute of Medical Biology
Singapore, Singapore City
National University of Singapore
Munro, Colin S.
United Kingdom, Glasgow
Southern General Hospital Glasgow
McLean, W. H.Irwin
United Kingdom, Dundee
University of Dundee
Statistics
Citations: 70
Authors: 32
Affiliations: 17
Identifiers
Doi:
10.1038/ng.2444
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Genetics And Genomics