Amer2 Protein Interacts with EB1 Protein and Adenomatous Polyposis Coli (APC) and Controls Microtubule Stability and Cell Migration

被引:15
作者
Pfister, Astrid S. [1 ]
Hadjihannas, Michel V. [1 ]
Roehrig, Waldemar [1 ]
Schambony, Alexandra [2 ]
Behrens, Juergen [1 ]
机构
[1] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Dept Biol, D-91058 Erlangen, Germany
关键词
PLASMA-MEMBRANE; BETA-CATENIN; WILMS-TUMOR; PLUS ENDS; BINDING; PHOSPHORYLATION; GSK3-BETA; DYNAMICS; POLARITY; GROWTH;
D O I
10.1074/jbc.M112.385393
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
EB1 is key factor in the organization of the microtubule cytoskeleton by binding to the plus-ends of microtubules and serving as a platform for a number of interacting proteins (termed +TIPs) that control microtubule dynamics. Together with its direct binding partner adenomatous polyposis coli (APC), EB1 can stabilize microtubules. Here, we show that Amer2 (APC membrane recruitment 2), a previously identified membrane-associated APC-binding protein, is a direct interaction partner of EB1 and acts as regulator of microtubule stability together with EB1. Amer2 binds to EB1 via specific (S/T)xIP motifs and recruits it to the plasma membrane. Coexpression of Amer2 and EB1 generates stabilized microtubules at the plasma membrane, whereas knockdown of Amer2 leads to destabilization of microtubules. Knockdown of Amer2, APC, or EB1 reduces cell migration, and morpholino-mediated down-regulation of Xenopus Amer2 blocks convergent extension cell movements, suggesting that the Amer2-EB1-APC complex regulates cell migration by altering microtubule stability.
引用
收藏
页码:35333 / 35340
页数:8
相关论文
共 30 条
[1]   Tracking the ends: a dynamic protein network controls the fate of microtubule tips [J].
Akhmanova, Anna ;
Steinmetz, Michel O. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (04) :309-322
[2]   Regulation and function of the interaction between the APC tumour suppressor protein and EB1 [J].
Askham, JM ;
Moncur, P ;
Markham, AF ;
Morrison, EE .
ONCOGENE, 2000, 19 (15) :1950-1958
[3]  
Barth AIM, 2002, J CELL SCI, V115, P1583
[4]   Functional interaction of an axin homolog, conductin, with β-catenin, APC, and GSK3β [J].
Behrens, J ;
Jerchow, BA ;
Würtele, M ;
Grimm, J ;
Asbrand, C ;
Wirtz, R ;
Kühl, M ;
Wedlich, D ;
Birchmeier, W .
SCIENCE, 1998, 280 (5363) :596-599
[5]   The WTX/AMER1 gene family: evolution, signature and function [J].
Boutet, Agnes ;
Comai, Glenda ;
Schedl, Andreas .
BMC EVOLUTIONARY BIOLOGY, 2010, 10
[6]   AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane [J].
Grohmann, Annette ;
Tanneberger, Kristina ;
Alzner, Astrid ;
Schneikert, Jean ;
Behrens, Jurgen .
JOURNAL OF CELL SCIENCE, 2007, 120 (21) :3738-3747
[7]   An EB1-Binding Motif Acts as a Microtubule Tip Localization Signal [J].
Honnappa, Srinivas ;
Gouveia, Susana Montenegro ;
Weisbrich, Anke ;
Damberger, Fred F. ;
Bhavesh, Neel S. ;
Jawhari, Hatim ;
Grigoriev, Ilya ;
van Rijssel, Frederik J. A. ;
Buey, Ruben M. ;
Lawera, Aleksandra ;
Jelesarov, Ilian ;
Winkler, Fritz K. ;
Wuethrich, Kurt ;
Akhmanova, Anna ;
Steinmetz, Michel O. .
CELL, 2009, 138 (02) :366-376
[8]   Adenomatous polyposis coli in cell extensions can promote with or without EB1 [J].
Kita, K ;
Wittmann, T ;
Näthke, IS ;
Waterman-Storer, CM .
MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (05) :2331-2345
[9]   Mammalian end binding proteins control persistent microtubule growth [J].
Komarova, Yulia ;
De Groot, Christian O. ;
Grigoriev, Ilya ;
Gouveia, Susana Montenegro ;
Munteanu, E. Laura ;
Schober, Joseph M. ;
Honnappa, Srinivas ;
Buey, Ruben M. ;
Hoogenraad, Casper C. ;
Dogterom, Marileen ;
Borisy, Gary G. ;
Steinmetz, Michel O. ;
Akhmanova, Anna .
JOURNAL OF CELL BIOLOGY, 2009, 184 (05) :691-706
[10]   Nucleo-cytoplasmic distribution of β-catenin is regulated by retention [J].
Krieghoff, E ;
Behrens, J ;
Mayr, B .
JOURNAL OF CELL SCIENCE, 2006, 119 (07) :1453-1463