Linked Life Data

16569658

Source:http://linkedlifedata.com/resource/pubmed/id/16569658

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 8
pubmed:dateCreated
2006-4-6
pubmed:abstractText
Differentiating neurons extend membrane protrusions that develop into growing neurites. The driving force for neurite outgrowth is the dynamic actin cytoskeleton, which is regulated by actin-binding proteins. In this study, we describe for the first time, the role of profilin I and its ligand interactions in neuritogenesis of PC12 cells. High-level overexpression of wild-type profilin I had an inhibitory effect on neurite outgrowth. Low levels of profilin I did not disturb this process, but these cells developed many more filopodia along the neurite shafts. Low-level overexpression of mutant forms of profilin I changed one or more aspects of PC12 differentiation. Expression of a profilin I mutant that is defective in actin binding (profilin I(R74E)) decreased neurite length and strongly inhibited filopodia formation. Cells expressing mutants defective in binding proline-rich ligands (profilin I(W3A) and profilin I(R136D)) differentiated faster, developed more and longer neurites and more branches. The profilin I(R136D) mutant, which is also defective in phosphatidylinositol 4,5-bisphosphate binding, enhanced neurite outgrowth even in the absence of NGF. Parental PC12 cells treated with the ROCK inhibitor Y27632, differentiate faster and display longer neurites and more branches. Similar effects were seen in cells expressing profilin I(WT), profilin I(W3A) and profilin I(R74E). By contrast, the profilin I(R136D)-expressing cells were insensitive to the ROCK inhibitor, suggesting that regulation of profilin I by phosphatidylinositol 4,5-bisphosphate metabolism is crucial for proper neurite outgrowth. Taken together, our data show the importance of the interaction of profilin I with actin, proline-rich proteins and phosphatidylinositol 4,5-bisphosphate in neuronal differentiation of PC12 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1570-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16569658-Animals, pubmed-meshheading:16569658-Cell Differentiation, pubmed-meshheading:16569658-Cell Enlargement, pubmed-meshheading:16569658-Dose-Response Relationship, Drug, pubmed-meshheading:16569658-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16569658-Ligands, pubmed-meshheading:16569658-Models, Biological, pubmed-meshheading:16569658-Neurites, pubmed-meshheading:16569658-PC12 Cells, pubmed-meshheading:16569658-Phalloidine, pubmed-meshheading:16569658-Phosphatidylinositol 4,5-Diphosphate, pubmed-meshheading:16569658-Profilins, pubmed-meshheading:16569658-Protein Binding, pubmed-meshheading:16569658-Protein-Serine-Threonine Kinases, pubmed-meshheading:16569658-Pseudopodia, pubmed-meshheading:16569658-Rats, pubmed-meshheading:16569658-Time Factors, pubmed-meshheading:16569658-Transfection, pubmed-meshheading:16569658-rho-Associated Kinases
pubmed:year
2006
pubmed:articleTitle
Profilin-I-ligand interactions influence various aspects of neuronal differentiation.
pubmed:affiliation
Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Belgium. anja.lambrechts@Ugent.be
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't