Localization and trafficking of receptors play a key role in their signalling capability. Indeed, receptor function is related to the microenvironment inside the cells, where specific signalling molecules are compartmentalized. Mislocalisation and/or altered trafficking of receptors frequently correlate with the activation of proliferative pathways leading to development of cancer. For example, rearrangements of TrkA, which produce mutants localized in the cytoplasm, are frequently found in thyroid carcinomas. While it is known that TrkA signalling can be regulated by its localization, the role of cellular localization of its co-receptor, p75NTR, in modulating the response to neurotrophins is still unclear. Lipid rafts, which are areas of membranes enriched in sphingolipids and cholesterol, are believed to function in cellular signalling by recruiting specific molecules in a unique lipid environment thus increasing the efficiency of signal transduction. In this proposal we will analyze the intracellular trafficking and signal transduction of p75 NTR and TrkA receptor and the role of rafts and caveolae in their sorting and signalling. Immediately after the first findings, we will further explore the relationship between subcellular compartmentalisation and cancer development. This project will provide to explain how a receptor involved in modulating a proliferative pathway is controlled by its intracellular compartmentalisation. Moreover this project will provide important clues to role of caveolin 1 both as modulator of signalling pathways and as anti-oncogene. All these findings will be relevant to understand the relationship between sorting and subcellular localization, signal transduction and the onset of cancer.

Role of rafts and caveolins in the sorting and signaling of growth factor receptor involved in thyroid cancer

PALADINO, SIMONA
2007

Abstract

Localization and trafficking of receptors play a key role in their signalling capability. Indeed, receptor function is related to the microenvironment inside the cells, where specific signalling molecules are compartmentalized. Mislocalisation and/or altered trafficking of receptors frequently correlate with the activation of proliferative pathways leading to development of cancer. For example, rearrangements of TrkA, which produce mutants localized in the cytoplasm, are frequently found in thyroid carcinomas. While it is known that TrkA signalling can be regulated by its localization, the role of cellular localization of its co-receptor, p75NTR, in modulating the response to neurotrophins is still unclear. Lipid rafts, which are areas of membranes enriched in sphingolipids and cholesterol, are believed to function in cellular signalling by recruiting specific molecules in a unique lipid environment thus increasing the efficiency of signal transduction. In this proposal we will analyze the intracellular trafficking and signal transduction of p75 NTR and TrkA receptor and the role of rafts and caveolae in their sorting and signalling. Immediately after the first findings, we will further explore the relationship between subcellular compartmentalisation and cancer development. This project will provide to explain how a receptor involved in modulating a proliferative pathway is controlled by its intracellular compartmentalisation. Moreover this project will provide important clues to role of caveolin 1 both as modulator of signalling pathways and as anti-oncogene. All these findings will be relevant to understand the relationship between sorting and subcellular localization, signal transduction and the onset of cancer.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/362140
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