Characterisation of tetraspanins Tspan9 and Tspan33

Haining, Elizabeth Jayne (2014). Characterisation of tetraspanins Tspan9 and Tspan33. University of Birmingham. Ph.D.

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Abstract

The tetraspanins are a large superfamily of membrane proteins that contribute to the organisation of other cell surface proteins through homo- and heterogeneous lateral interactions. In platelets four of the 33 mammalian tetraspanins have been found to participate in mechanisms that regulate platelet sensitivity and activation. Tspan9 was recently discovered as a new platelet tetraspanin using an antibody and is highly expressed on platelets when compared to other tissues. Tspan33 was another new platelet tetraspanin identified by membrane proteomic approach. Neither tetraspanin had yet been functionally characterised on platelets and so their contribution to platelet biology was unknown. The aims of this thesis were to investigate the function ofTspan9 and Tspan33 in platelets using their respective knockout mice. The conclusion of this thesis was twofold. Firstly that Tspan33 is a member of the TspanC8 subfamily of tetraspanins that regulate the metalloprotease ADAMI 0, but is likely not expressed on mouse platelets. Secondly, Tspan9 promotes platelet activation through the collagen receptor GPVI by regulating its membrane dynamics. These novel regulatory mechanisms for ADAMI 0 and GPVI offer new avenues of research into therapy for diseases such as Alzheimer's disease and atherosclerosis in which ADAM I 0 and GPVI respectively play central roles.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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