2.50
Hdl Handle:
http://hdl.handle.net/10033/218377
Title:
Essential role for Abi1 in embryonic survival and WAVE2 complex integrity.
Authors:
Dubielecka, Patrycja M; Ladwein, Kathrin I; Xiong, Xiaoling; Migeotte, Isabelle; Chorzalska, Anna; Anderson, Kathryn V; Sawicki, Janet A; Rottner, Klemens; Stradal, Theresia E; Kotula, Leszek
Abstract:
Abl interactor 1 (Abi1) plays a critical function in actin cytoskeleton dynamics through participation in the WAVE2 complex. To gain a better understanding of the specific role of Abi1, we generated a conditional Abi1-KO mouse model and MEFs lacking Abi1 expression. Abi1-KO cells displayed defective regulation of the actin cytoskeleton, and this dysregulation was ascribed to altered activity of the WAVE2 complex. Changes in motility of Abi1-KO cells were manifested by a decreased migration rate and distance but increased directional persistence. Although these phenotypes did not correlate with peripheral ruffling, which was unaffected, Abi1-KO cells exhibited decreased dorsal ruffling. Western blotting analysis of Abi1-KO cell lysates indicated reduced levels of the WAVE complex components WAVE1 and WAVE2, Nap1, and Sra-1/PIR121. Although relative Abi2 levels were more than doubled in Abi1-KO cells, the absolute Abi2 expression in these cells amounted only to a fifth of Abi1 levels in the control cell line. This finding suggests that the presence of Abi1 is critical for the integrity and stability of WAVE complex and that Abi2 levels are not sufficiently increased to compensate fully for the loss of Abi1 in KO cells and to restore the integrity and function of the WAVE complex. The essential function of Abi1 in WAVE complexes and their regulation might explain the observed embryonic lethality of Abi1-deficient embryos, which survived until approximately embryonic day 11.5 and displayed malformations in the developing heart and brain. Cells lacking Abi1 and the conditional Abi1-KO mouse will serve as critical models for defining Abi1 function.
Affiliation:
Laboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA.
Citation:
Essential role for Abi1 in embryonic survival and WAVE2 complex integrity. 2011, 108 (17):7022-7 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
26-Apr-2011
URI:
http://hdl.handle.net/10033/218377
DOI:
10.1073/pnas.1016811108
PubMed ID:
21482783
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
Publications of RG Signalling and Motility (SIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorDubielecka, Patrycja Men_GB
dc.contributor.authorLadwein, Kathrin Ien_GB
dc.contributor.authorXiong, Xiaolingen_GB
dc.contributor.authorMigeotte, Isabelleen_GB
dc.contributor.authorChorzalska, Annaen_GB
dc.contributor.authorAnderson, Kathryn Ven_GB
dc.contributor.authorSawicki, Janet Aen_GB
dc.contributor.authorRottner, Klemensen_GB
dc.contributor.authorStradal, Theresia Een_GB
dc.contributor.authorKotula, Leszeken_GB
dc.date.accessioned2012-04-13T13:42:12Z-
dc.date.available2012-04-13T13:42:12Z-
dc.date.issued2011-04-26-
dc.identifier.citationEssential role for Abi1 in embryonic survival and WAVE2 complex integrity. 2011, 108 (17):7022-7 Proc. Natl. Acad. Sci. U.S.A.en_GB
dc.identifier.issn1091-6490-
dc.identifier.pmid21482783-
dc.identifier.doi10.1073/pnas.1016811108-
dc.identifier.urihttp://hdl.handle.net/10033/218377-
dc.description.abstractAbl interactor 1 (Abi1) plays a critical function in actin cytoskeleton dynamics through participation in the WAVE2 complex. To gain a better understanding of the specific role of Abi1, we generated a conditional Abi1-KO mouse model and MEFs lacking Abi1 expression. Abi1-KO cells displayed defective regulation of the actin cytoskeleton, and this dysregulation was ascribed to altered activity of the WAVE2 complex. Changes in motility of Abi1-KO cells were manifested by a decreased migration rate and distance but increased directional persistence. Although these phenotypes did not correlate with peripheral ruffling, which was unaffected, Abi1-KO cells exhibited decreased dorsal ruffling. Western blotting analysis of Abi1-KO cell lysates indicated reduced levels of the WAVE complex components WAVE1 and WAVE2, Nap1, and Sra-1/PIR121. Although relative Abi2 levels were more than doubled in Abi1-KO cells, the absolute Abi2 expression in these cells amounted only to a fifth of Abi1 levels in the control cell line. This finding suggests that the presence of Abi1 is critical for the integrity and stability of WAVE complex and that Abi2 levels are not sufficiently increased to compensate fully for the loss of Abi1 in KO cells and to restore the integrity and function of the WAVE complex. The essential function of Abi1 in WAVE complexes and their regulation might explain the observed embryonic lethality of Abi1-deficient embryos, which survived until approximately embryonic day 11.5 and displayed malformations in the developing heart and brain. Cells lacking Abi1 and the conditional Abi1-KO mouse will serve as critical models for defining Abi1 function.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Proceedings of the National Academy of Sciences of the United States of Americaen_GB
dc.subject.meshAdaptor Proteins, Signal Transducingen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBrainen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshCell Movementen_GB
dc.subject.meshCytoskeletal Proteinsen_GB
dc.subject.meshEmbryo, Mammalianen_GB
dc.subject.meshHearten_GB
dc.subject.meshHomeodomain Proteinsen_GB
dc.subject.meshMembrane Proteinsen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshMultiprotein Complexesen_GB
dc.subject.meshWiskott-Aldrich Syndrome Protein Familyen_GB
dc.titleEssential role for Abi1 in embryonic survival and WAVE2 complex integrity.en
dc.typeArticleen
dc.contributor.departmentLaboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA.en_GB
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen_GB

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.