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Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo.

Kenzelmann D, Chiquet-Ehrismann R, Leachman NT, Tucker RP - BMC Dev. Biol. (2008)

Bottom Line: Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information.Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.

View Article: PubMed Central - HTML - PubMed

Affiliation: Friedrich Miescher Institute, Novartis Research Foundation, Maulbeerstr. 66, 4057 Basel, Switzerland. daniela.kenzelmann@fmi.ch

ABSTRACT

Background: Teneurins are a unique family of transmembrane proteins conserved from C. elegans and D. melanogaster to mammals. In vertebrates there are four paralogs (teneurin-1 to -4), all of which are expressed prominently in the developing central nervous system.

Results: Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity. In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.

Conclusion: Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.

Show MeSH
Model of teneurin signalling. This model describes how an intracellular domain (ICD) could be generated from a transmembrane protein and transported to the nucleus. This process takes place only in specific cells and tissues where the anti-ICD labeled nuclei. 1) A first protease sheds the extracellular domain (ECD) of teneurins. 2) The remainder of teneurin-1 can now become a substrate for an intramembrane protease. 3) The ICD is released. 4) The soluble ICD translocates to the nucleus via nuclear localization signal (NLS). EGF, EGF-like repeats; YD, YD-repeats. Red arrows indicate postulated cleavage sites and the yellow spheres proteins interacting with teneurin-1 ICD in the nucleus.
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Figure 6: Model of teneurin signalling. This model describes how an intracellular domain (ICD) could be generated from a transmembrane protein and transported to the nucleus. This process takes place only in specific cells and tissues where the anti-ICD labeled nuclei. 1) A first protease sheds the extracellular domain (ECD) of teneurins. 2) The remainder of teneurin-1 can now become a substrate for an intramembrane protease. 3) The ICD is released. 4) The soluble ICD translocates to the nucleus via nuclear localization signal (NLS). EGF, EGF-like repeats; YD, YD-repeats. Red arrows indicate postulated cleavage sites and the yellow spheres proteins interacting with teneurin-1 ICD in the nucleus.

Mentions: In this study we show that teneurin-1 is expressed in interconnected regions of the developing chick brain, and its expression pattern is complementary to teneurin-2. We present the first evidence of teneurin processing in vertebrates and demonstrate that the ICD of teneurin-1 contains a functional NLS. Our results provide support for the hypothesis that teneurins can be proteolytically processed to generate a soluble ICD that translocates to the nucleus (Fig. 6).


Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo.

Kenzelmann D, Chiquet-Ehrismann R, Leachman NT, Tucker RP - BMC Dev. Biol. (2008)

Model of teneurin signalling. This model describes how an intracellular domain (ICD) could be generated from a transmembrane protein and transported to the nucleus. This process takes place only in specific cells and tissues where the anti-ICD labeled nuclei. 1) A first protease sheds the extracellular domain (ECD) of teneurins. 2) The remainder of teneurin-1 can now become a substrate for an intramembrane protease. 3) The ICD is released. 4) The soluble ICD translocates to the nucleus via nuclear localization signal (NLS). EGF, EGF-like repeats; YD, YD-repeats. Red arrows indicate postulated cleavage sites and the yellow spheres proteins interacting with teneurin-1 ICD in the nucleus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2289808&req=5

Figure 6: Model of teneurin signalling. This model describes how an intracellular domain (ICD) could be generated from a transmembrane protein and transported to the nucleus. This process takes place only in specific cells and tissues where the anti-ICD labeled nuclei. 1) A first protease sheds the extracellular domain (ECD) of teneurins. 2) The remainder of teneurin-1 can now become a substrate for an intramembrane protease. 3) The ICD is released. 4) The soluble ICD translocates to the nucleus via nuclear localization signal (NLS). EGF, EGF-like repeats; YD, YD-repeats. Red arrows indicate postulated cleavage sites and the yellow spheres proteins interacting with teneurin-1 ICD in the nucleus.
Mentions: In this study we show that teneurin-1 is expressed in interconnected regions of the developing chick brain, and its expression pattern is complementary to teneurin-2. We present the first evidence of teneurin processing in vertebrates and demonstrate that the ICD of teneurin-1 contains a functional NLS. Our results provide support for the hypothesis that teneurins can be proteolytically processed to generate a soluble ICD that translocates to the nucleus (Fig. 6).

Bottom Line: Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information.Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.

View Article: PubMed Central - HTML - PubMed

Affiliation: Friedrich Miescher Institute, Novartis Research Foundation, Maulbeerstr. 66, 4057 Basel, Switzerland. daniela.kenzelmann@fmi.ch

ABSTRACT

Background: Teneurins are a unique family of transmembrane proteins conserved from C. elegans and D. melanogaster to mammals. In vertebrates there are four paralogs (teneurin-1 to -4), all of which are expressed prominently in the developing central nervous system.

Results: Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity. In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.

Conclusion: Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.

Show MeSH