Cross-linking of phospholipid membranes is a conserved property of calcium-sensitive synaptotagmins

被引：23

作者：

Connell, Emma ^{[1
]}

Giniatullina, Asiya ^{[1
,2
]}

Lai-Kee-Him, Josephine ^{[3
]}

Tavare, Richard ^{[1
]}

Ferrari, Eurico ^{[2
]}

Roseman, Alan ^{[1
,4
]}

Cojoc, Dan ^{[2
]}

Brisson, Alain R. ^{[3
]}

Davletov, Bazbek ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

[2] CNR, INFM, Lab Nazl TASC, I-34012 Trieste, Italy

[3] Univ Bordeaux, CNRS, IECB, UMR 5248, F-33405 Talence, France

[4] Univ Manchester, Fac Life Sci, Manchester, Lancs, England

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2008年 / 380卷 / 01期

基金：

英国医学研究理事会;

关键词：

C2; domain; membrane cross-linking; synaptotagmin; electron microscopy; laser trap;

D O I：

10.1016/j.jmb.2008.01.084

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：

Synaptotagmins are vesicular proteins implicated in many membrane trafficking events. They are highly conserved in evolution and the mammalian family contains 16 isoforms. We now show that the tandem C2 domains of several calcium-sensitive synaptotagmin isoforms tested, including Drosophila synaptotagmin, rapidly cross-link phospholipid membranes. In contrast to the tandem structure, individual C2 domains failed to trigger membrane cross-linking in several novel assays. Large-scale liposomal aggregation driven by tandem C2 domains in response to calcium was confirmed by the following techniques: turbidity assay, dynamic light-scattering and both confocal and negative stain electron microscopy. Firm cross-linking of membranes was evident from laser trap experiments. High-resolution cryo-electron microscopy revealed that membrane cross-linking by tandem C2 domains results in a constant distance of similar to 9 rum between the apposed membranes. Our findings show the conserved nature of this important property of synaptotagmin, demonstrate the significance of the tandem C2 domain structure and provide a plausible explanation for the accelerating effect of synaptotagmins on membrane fusion. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：42 / 50

页数：9

共 39 条

[1] Synaptotagmin IV is necessary for the maturation of secretory granules in PC12 cells [J].