Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-27
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Abi1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Abi2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes, http://linkedlifedata.com/resource/pubmed/chemical/Nap1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Sra-1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Wasf2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Wiskott-Aldrich Syndrome Protein...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7022-7
pubmed:dateRevised
2011-10-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Essential role for Abi1 in embryonic survival and WAVE2 complex integrity.
pubmed:affiliation
Laboratory of Cell Signaling, New York Blood Center, New York, NY 10065, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural