Strategies to interfere with PDZ-mediated interactions in neurons: What we can learn from the rabies virus

被引：22

作者：

Caillet-Saguy, Celia ^{[1
]}

Maisonneuve, Pierre ^{[1
]}

Delhommel, Florent ^{[1
,2
]}

Terrien, Elouan ^{[1
]}

Babault, Nicolas ^{[1
]}

Lafon, Monique ^{[3
]}

Cordier, Florence ^{[1
]}

Wolff, Nicolas ^{[1
]}

机构：

[1] Inst Pasteur, Dept Biol Struct & Chim, Unite RMN Biomol, CNRS UMR 3528, F-75724 Paris 15, France

[2] Univ Paris 06, Cellule Pasteur UPMC, F-75015 Paris, France

[3] Inst Pasteur, Dept Virol, Unite Neuroimmunol Virale, F-75724 Paris 15, France

来源：

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY | 2015年 / 119卷 / 01期

关键词：

PDZ domain; Rabies virus; Neurons; Neuronal signaling; Phosphorylation; Enzymatic regulation; PROTEIN STABILITY; DOMAIN; PTEN; PHOSPHORYLATION; IDENTIFICATION; BRAIN; DYNAMICS; RECEPTOR; TARGETS; BINDING;

D O I：

10.1016/j.pbiomolbio.2015.02.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

PDZ (PSD-95/Dlg/ZO-1) domains play a major role in neuronal homeostasis in which they act as scaffold domains regulating cellular trafficking, self-association and catalytic activity of essential proteins such as kinases and phosphatases. Because of their central role in cell signaling, cellular PDZ-containing proteins are preferential targets of viruses to hijack cellular function to their advantage. Here, we describe how the viral G protein of the rabies virus specifically targets the PDZ domain of neuronal enzymes during viral infection. By disrupting the complexes formed by cellular enzymes and their ligands, the virus triggers drastic effect on cell signaling and commitment of the cell to either survival (virulent strains) or death (vaccinal strains). We provide structural and biological evidences that the viral proteins act as competitors endowed with specificity and affinity in an essential cellular process by mimicking PDZ binding motif of cellular partners. Disruption of critical endogenous protein protein interactions by viral protein drastically alters intracellular protein trafficking and catalytic activity of cellular proteins that control cell homeostasis. This work opens up many perspectives to mimic viral sequences and developing innovative therapies to manipulate cellular homeostasis. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：53 / 59

页数：7

共 36 条

[1] Peptides Targeting the PDZ Domain of PTPN4 Are Efficient Inducers of Glioblastoma Cell Death [J].