Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance

被引：0

作者：

K Duning

D O Wennmann

A Bokemeyer

C Reissner

H Wersching

C Thomas

J Buschert

K Guske

V Franzke

A Flöel

H Lohmann

S Knecht

S-M Brand

M Pöter

U Rescher

M Missler

P Seelheim

C Pröpper

T M Boeckers

L Makuch

R Huganir

T Weide

E Brand

H Pavenstädt

J Kremerskothen

机构：

[1] Internal Medicine D,Department of Nephrology

[2] Hypertension and Rheumatology,Department of Anatomy and Molecular Neurobiology

[3] University Hospital Münster,Department of Neurology

[4] University Münster,undefined

[5] Institute of Epidemiology and Social Medicine,undefined

[6] University of Münster,undefined

[7] University Hospital Münster,undefined

[8] Institute of Sports Medicine,undefined

[9] University of Münster,undefined

[10] Institute of Medical Biochemistry,undefined

[11] Center for Molecular Biology of Inflammation,undefined

[12] Institute of Biochemistry,undefined

[13] University of Münster,undefined

[14] Institute of Anatomy and Cell Biology,undefined

[15] University Ulm,undefined

[16] Howard Hughes Medical Center,undefined

[17] John Hopkins University,undefined

[18] 11Current address: Department of Neurology,undefined

[19] Center for Stroke Research Berlin,undefined

[20] Cluster of Excellence NeuroCure,undefined

[21] Charite Universitätsmedizin,undefined

[22] Berlin,undefined

[23] Germany.,undefined

来源：

Translational Psychiatry | 2013年 / 3卷

关键词：

C2 domain; human cognition; KIBRA; membrane binding; phosphatidylinositols;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer’s disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct Ca2+ dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.

引用

页码：e272 / e272

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