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Molecular characterisation of CRYPα, an axonal receptor protein tyrosine phosphatase

Aricescu, Alexandru Radu; (2001) Molecular characterisation of CRYPα, an axonal receptor protein tyrosine phosphatase. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Receptor protein tyrosine phosphatases (RPTPs) represent a major research focus in developmental biology, oncology and immunology. Specifically, cell adhesion molecule-like RPTPs, including CRYPα, have recently emerged as key regulators of nervous system development, being involved in axonal growth and guidance, and nerve repair. However, very little is known about their signal transduction mechanisms since the identity of various interacting molecules is far from being completely elucidated. In this thesis I demonstrate that CRYPα has a novel, heparin-binding activity and that its interaction with the retinal basal lamina is mediated by the heparan sulphate chains of extracellular matrix proteoglycans. Using molecular modelling and site-directed mutagenesis, I have mapped the heparin/heparan sulphate binding site in the first immunoglobulin-like domain of CRYPα. I also describe the first identification of heterotypic ligands for a type II neural RPTP, namely the secreted isoforms of agrin and collagen XVIII. Given the broad functional spectrum of these molecules, a novel perspective towards understanding CRYPα's functions and regulation has been opened. In addition, it became apparent that this RPTP itself can be phosphorylated in vivo and preliminary experiments suggest the existence of a ~75 kDa putative substrate for its enzymatic activity. Altogether, these data contribute to the molecular characterisation of CRYPα and suggest potential ways to modulate its signalling function in pathological conditions.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Molecular characterisation of CRYPα, an axonal receptor protein tyrosine phosphatase
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Phosphotases; Receptor protein
URI: https://discovery.ucl.ac.uk/id/eprint/10102944
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