Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.697407
Title: Characterisation of the voltage gated proton channel HVCN1 in B cells
Author: Bhamrah, Mandeep Kaur
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2011
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Abstract:
HVCN1 is a voltage-gated proton channel, detected in a proteomic screen profiling membrane proteins of Mantle Cell Lymphoma cells. Subsequent analysis showed that HVCN1 is expressed in naive mature resting B cells, such as cells of Mantle Zones in lymph nodes and circulating peripheral B cells. The role of voltage-proton channels in B cells is unknown and further characterized in this study. HVCN1 co-localizes with the BCR and markers of MIIC vesicles and translocates with the BCR upon internalization of receptor-antigen complexes. Mass spectrometry data confirmed key proteins involved in BCR signalling, such as IgM, CD79B (Igp), CD19 and CD22 were associated with HVCN1 at a resting and stimulated state of the cell, demonstrating HVCN1 functioned in the regulation of B-cell receptor signalling. BCR stimulation has shown to result in the production of ROS, which can regulate B-cell activation, through the oxidation of Protein Tyrosine Phosphatases. Primary B cells isolated from mice lacking HVCN1 demonstrated weak signalling following cross-linking of the BCR with anti-IgM, which was rescued in the presence of the Sodium Stibogluconate, an inhibitor of the CD22 associated phosphatase SHP-1. The catalytic activity of phosphatases was reduced by ROS and allowed phosphorylation of protein, which was regulated through a negative signalling feedback loop. Lack of HVCN1 dampened the phosphorylation of key signalling molecules SYK and AKT, involved in the activation and proliferation of B cells. Therefore, HVCN1 functions to modulate the balance of ROS production in the cell upon BCR activation, allowing the effective transmission of signalling in the cell.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.697407  DOI: Not available
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