Amer2 protein interacts with EB1 protein and adenomatous polyposis coli (APC) and controls microtubule stability and cell migration.
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.
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuremberg, 91054 Erlangen.
Astrid S
AS
Pfister
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuremberg, 91054 Erlangen.
Michel V
MV
Hadjihannas
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuremberg, 91054 Erlangen.
Waldemar
W
Röhrig
Biology Department, Developmental Biology, University Erlangen-Nuremberg, 91058 Erlangen, Germany.
Alexandra
A
Schambony
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuremberg, 91054 Erlangen. Electronic address: jbehrens@molmed.uni-erlangen.de.
Jürgen
J
Behrens
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
C570412:AMER2 protein, human; C555337:APC protein, human; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; C500985:MAPRE1 protein, human; C561584:Mapre1 protein, rat; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins