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Title: Characterisation of the expression and function of ADAM23
Author: Goldsmith, Alexander Patrick
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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Several members of the ADAM (a disintegrin and metalloprotease) family of cell-surface proteins have been implicated in biological processes ranging from fertilisation to myoblast fusion and neural cell fate determination. While proteins have so far been studied mostly in terms of their protease activity, there is a considerable amount of evidence to suggest that many ADAMs are important as receptors for transmembrane molecules, such as integrins, and extracellular matrix components. Indeed, around half of all known ADAMs are proteolyitcally inactive. We are interested in the question of whether ADAMs serve as integrin ligands in the nervous system, and the following report describes our efforts to address this issue with specific reference to ADAM23. We have shown that ADAM23 mRNA is expressed in neuronal cells throughout the rat brain, at all stages of postnatal development, and that particularly high transcript concentrations are found in the hippocampus and cerebellum. Using an antibody that we raised against the rat ADAM23 disintegrin domain, we have found that ADAM23 is present at detectable levels only in nervous system tissue. Our analysis of ADAM23 expression in cultured cerebellar granule cells (CGCs) furthermore suggests that this protein is synthesised as a glycosylated precursor of around 100kD whose maturation depends on cleavage by furin or a related enzyme. We have also found ADAM23 to be expressed primarily as a cell-surface protein that may become localised to sites of intercellular contact. Finally, we have attempted to define the protein’s function by analysing brain tissue from ADAM23-null mice, which have previously been shown to exhibit a ataxic phenotype suggestive of cerebellar defects. We have found that ADAM23-null brains appear morphologically normal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available