Source:http://linkedlifedata.com/resource/pubmed/id/11438594
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
14
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| pubmed:dateCreated |
2001-7-4
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| pubmed:abstractText |
Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha2-chimaerin mRNA expression resembles that of cyclin-dependent kinase regulator p35 (CDK5/p35) which participates in neuronal differentiation and with which chimaerin interacts. To determine whether alpha2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. When plated on poly-lysine, transient alpha2-chimaerin but not alpha1-chimaerin transfectants formed neurites. Permanent alpha2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha2-chimaerin mutated in the SH2 domain (N94H) generated an alpha1-chimaerin-like phenotype, protein partitioned in the particulate fraction, and in NGF-stimulated pheochromocytoma cell line 12 (PC12) cells, neurite formation was inhibited. These results indicate a role for alpha2-chimaerin in morphological differentiation for which its SH2 domain is vital.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chimerin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/cdc42 GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
21
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5191-202
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11438594-Aging,
pubmed-meshheading:11438594-Alternative Splicing,
pubmed-meshheading:11438594-Animals,
pubmed-meshheading:11438594-COS Cells,
pubmed-meshheading:11438594-Cell Differentiation,
pubmed-meshheading:11438594-Chimerin 1,
pubmed-meshheading:11438594-Entorhinal Cortex,
pubmed-meshheading:11438594-In Situ Hybridization,
pubmed-meshheading:11438594-Mice,
pubmed-meshheading:11438594-Mutagenesis, Site-Directed,
pubmed-meshheading:11438594-Nervous System,
pubmed-meshheading:11438594-Neurites,
pubmed-meshheading:11438594-Neuroblastoma,
pubmed-meshheading:11438594-Organ Specificity,
pubmed-meshheading:11438594-PC12 Cells,
pubmed-meshheading:11438594-Protein Isoforms,
pubmed-meshheading:11438594-RNA, Messenger,
pubmed-meshheading:11438594-Rats,
pubmed-meshheading:11438594-Rats, Sprague-Dawley,
pubmed-meshheading:11438594-Subcellular Fractions,
pubmed-meshheading:11438594-Transfection,
pubmed-meshheading:11438594-cdc42 GTP-Binding Protein,
pubmed-meshheading:11438594-rac1 GTP-Binding Protein,
pubmed-meshheading:11438594-src Homology Domains
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| pubmed:year |
2001
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| pubmed:articleTitle |
alpha2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells.
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| pubmed:affiliation |
Department of Neurochemistry, Institute of Neurology, University College London, London WC1N 1PJ, United Kingdom.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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