Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA.
J Biol Chem. 2010 Apr 23;285(17):13022-31. doi: 10.1074/jbc.M109.079426. Epub 2010 Feb 22.
A family of integral membrane proteins containing a signature DHHC motif has been shown to display protein S-acyltransferase activity, modifying cysteine residues in proteins with fatty acids. The physiological roles of these proteins have largely been unexplored. Here we report that mice homozygous for a hypomorphic allele of a previously uncharacterized member, DHHC5, are born at half the expected rate, and survivors show a marked deficit in contextual fear conditioning, an indicator of defective hippocampal-dependent learning. DHHC5 is highly enriched in a post-synaptic density preparation and co-immunoprecipitates with post-synaptic density protein-95 (PSD-95), an interaction that is mediated through binding of the carboxyl terminus of DHHC5 and the PDZ3 domain of PSD-95. Immunohistochemistry demonstrated that DHHC5 is expressed in the CA3 and dentate gyrus in the hippocampus. These findings point to a previously unsuspected role for DHHC5 in post-synaptic function affecting learning and memory.
一个包含特征性 DHHC 基序的完整膜蛋白家族已被证明具有蛋白质 S-酰基转移酶活性，可将脂肪酸修饰到蛋白质中的半胱氨酸残基上。这些蛋白质的生理作用在很大程度上尚未得到探索。在这里，我们报告说，以前未被表征的成员 DHHC5 的一个功能不全等位基因的纯合子小鼠的出生率仅为预期的一半，而存活下来的小鼠在情景性恐惧条件反射方面表现出明显的缺陷，这是海马依赖型学习缺陷的一个指标。DHHC5 在突触后密度制剂中高度富集，并与突触后密度蛋白-95 (PSD-95) 共免疫沉淀，这种相互作用是通过 DHHC5 的羧基末端与 PSD-95 的 PDZ3 结构域的结合介导的。免疫组织化学显示 DHHC5 在海马体的 CA3 和齿状回中表达。这些发现表明 DHHC5 在影响学习和记忆的突触后功能中具有以前未被怀疑的作用。
