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Leukocyte common antigen-related receptor-linked tyrosine phosphatase. Regulation of mRNA expression
F M Longo1, J A Martignetti, J M Le Beau
1Department of Neurology, University of California/Veterans Affairs Medical Center, San Francisco 94121.
Abstract:
Receptor-linked tyrosine phosphatases regulate cell growth by dephosphorylating proteins involved in tyrosine kinase signal transduction. Within this gene family, the leukocyte common antigen-related (LAR) gene is of particular interest with respect to the nervous system because it has sequence similarity to the neural cell adhesion molecule N-CAM and is located in a chromosomal region (1p32-33) frequently deleted in neuroectodermal tumors. However, immunostaining has detected LAR in non-neural tissues, but not in the central nervous system, peripheral neurons, or adrenal medulla. In this study, rat brain cDNA library LAR clones corresponding to cytoplasmic and 3'-untranslated regions of human LAR were identified. Using probes derived from these clones, high stringency Northern blots revealed approximately 8 kilobase and variable length tissue- and cell-specific LAR transcripts in cortex, brainstem, cerebellum, spinal cord, peripheral tissues, and cultured neural, glial, and pheochromocytoma cells. In situ hybridization showed expression by brain and dorsal root ganglion neurons. LAR expression was developmentally regulated in a region-dependent manner. Changes in LAR expression were also found during nerve growth factor-induced PC12 pheochromocytoma cell differentiation and with contact-mediated inhibition of fibroblast growth. These observations and studies demonstrating neurotrophins functioning via tyrosine kinase receptors suggest that LAR represents an additional mechanism regulating neural development.
Insights
Leukocyte common antigen-related (LAR) gene expression was detected in the rat nervous system, contrary to previous findings. LAR is developmentally regulated and changes with cell differentiation, suggesting a role in neural development.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Receptor-linked tyrosine phosphatases regulate cell growth via tyrosine kinase signaling.
- Leukocyte common antigen-related (LAR) gene is structurally similar to N-CAM and located in a region prone to neuroectodermal tumor deletion.
- Previous studies indicated LAR is absent in the central nervous system, peripheral neurons, and adrenal medulla.
Purpose of the Study:
- To investigate the presence and expression patterns of the leukocyte common antigen-related (LAR) gene in the rat nervous system.
- To determine the role of LAR in neural development and cell differentiation.
Main Methods:
- Identified rat brain cDNA clones for LAR.
- Utilized Northern blots to analyze LAR transcript expression in various tissues and cell types.
- Employed in situ hybridization to localize LAR expression in the brain and dorsal root ganglia.
- Observed changes in LAR expression during nerve growth factor-induced differentiation of PC12 cells and fibroblast growth inhibition.
Main Results:
- Detected tissue- and cell-specific LAR transcripts in multiple regions of the rat brain, spinal cord, and peripheral tissues.
- Confirmed LAR expression in cultured neural cells, glial cells, and pheochromocytoma cells.
- Demonstrated that LAR expression is developmentally regulated in a region-specific manner.
- Observed altered LAR expression during PC12 cell differentiation and fibroblast growth inhibition.
Conclusions:
- The leukocyte common antigen-related (LAR) gene is expressed in the rat nervous system, challenging previous assumptions.
- LAR expression is dynamic and regulated during neural development and cell differentiation.
- LAR may play a significant role in regulating neural development, potentially through pathways involving neurotrophins and tyrosine kinase receptors.