Hall, C.;
Michael, G.J.;
Cann, N.;
Ferrari, G.;
Teo, M.;
Jacobs, T.;
Monfries, C.;
(2001)
alpha 2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells.
The Journal of Neuroscience
, 21
(14)
pp. 5191-5202.
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Abstract
Neuronal differentiation involves Rac and Cdc42 GTPases. alpha -Chimaerin, a Rac/Cdc42 regulator, occurs as alpha 1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha 2-isoforms. alpha 2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha 1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha 2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha 2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha 2-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 alpha 2-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 alpha 2-chimaerin but not alpha 1-chimaerin transfectants formed neurites. Permanent alpha 2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha 1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha 2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha 1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha 2-chimaerin mutated in the SH2 domain (N94H) generated an alpha 1-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 alpha 2-chimaerin in morphological differentiation for which its SH2 domain is vital.
| Type: | Article |
|---|---|
| Title: | alpha 2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://www.jneurosci.org/cgi/content/abstract/21/1... |
| Language: | English |
| Additional information: | Copyright Society for Neuroscience 2001 This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. |
| Keywords: | alpha 2-chimaerin, Rac, Cdc42, GTPase, GAP, SH2, neurite outgrowth, embryonic brain, N1E-115 neuroblastoma, PC12, cdk5/p35, Crmp |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/7412 |
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