Title |
An N-Terminal Missense Mutation in STX11 Causative of FHL4 Abrogates Syntaxin-11 Binding to Munc18-2
|
---|---|
Published in |
Frontiers in immunology, January 2014
|
DOI | 10.3389/fimmu.2013.00515 |
Pubmed ID | |
Authors |
Martha-Lena Müller, Samuel C. C. Chiang, Marie Meeths, Bianca Tesi, Miriam Entesarian, Daniel Nilsson, Stephanie M. Wood, Magnus Nordenskjöld, Jan-Inge Henter, Ahmed Naqvi, Yenan T. Bryceson |
Abstract |
Familial hemophagocytic lymphohistiocytosis (FHL) is an often-fatal hyperinflammatory disorder caused by autosomal recessive mutations in PRF1, UNC13D, STX11, and STXBP2. We identified a homozygous STX11 mutation, c.173T > C (p.L58P), in three patients presenting clinically with hemophagocytic lymphohistiocytosis from unrelated Pakistani families. The mutation yields an amino acid substitution in the N-terminal Habc domain of syntaxin-11 and resulted in defective natural killer cell degranulation. Notably, syntaxin-11 expression was decreased in patient cells. However, in an ectopic expression system, syntaxin-11 L58P was expressed at levels comparable to wild-type syntaxin-11, but did not bind Munc18-2. Moreover, another N-terminal syntaxin-11 mutant, R4A, also did not bind Munc18-2. Thus, we have identified a novel missense STX11 mutation causative of FHL type 4. The syntaxin-11 R4A and L58P mutations reveal that both the N-terminus and Habc domain of syntaxin-11 are required for binding to Munc18-2, implying similarity to the dynamic binary binding of neuronal syntaxin-1 to Munc18-1. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Switzerland | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | 3% |
Unknown | 33 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 5 | 15% |
Student > Master | 4 | 12% |
Professor > Associate Professor | 4 | 12% |
Researcher | 4 | 12% |
Student > Doctoral Student | 2 | 6% |
Other | 2 | 6% |
Unknown | 13 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 10 | 29% |
Agricultural and Biological Sciences | 6 | 18% |
Immunology and Microbiology | 2 | 6% |
Medicine and Dentistry | 2 | 6% |
Neuroscience | 1 | 3% |
Other | 0 | 0% |
Unknown | 13 | 38% |