Title

Regulation of axon growth and guidance by receptor tyrosine phosphatases (RPTPs) during the development of the vertebrate nervous system

Date of Award

2000

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Molecular and Cellular Pharmacology

First Committee Member

John L. Bixby, Committee Chair

Abstract

Appropriate regulation of tyrosine phosphorylation is essential for axon growth and guidance. Evidence from invertebrates indicates that receptor type tyrosine phosphatases (RPTPs) are required for correct axon growth during CNS development. Two RPTPs, CRYP-2 and PTP-delta, have been shown to be expressed abundantly during the development of the nervous system in vertebrates. PTP-delta has a cell adhesion molecule-like extracellular domain (ECD) comprising 3 immunoglobulin (Ig) repeats and 8 fibronectin (FN) type III repeats whereas CRYP-2 has an extracellular domain containing 8 FN type III repeats only. The expression patterns of CRYP-2 and PTP-delta suggest that they may play important roles in neural development. To explore the functions of these two RPTPs, the extracellular domains of these two RPTPs were fused to the Fc portions of mIgG-1 and the fusion proteins were expressed in a eukoryotic expression system. Purified proteins were used as ligands to examine the functions of these RPTPs in vitro. CRYP-2 and PTP-delta exert different effects on neuronal adhesion and axon outgrowth. PTP-delta is a homophilic binding cell adhesion molecule and promotes neurite outgrowth from CNS neurons. CRYP-2, on the other hand, may have heretophilic binding partner(s). CRYP-2 is anti-adhesive for neuron cell bodies and inhibits laminin-induced neurite outgrowth from retina neurons in vitro. These results suggest that members of different subgroup RPTPs may exert different effects on axon growth and guidance in vivo. The competition and coordination of different RPTPs in local environment are likely to be important for directed axon growth during the development of the vertebrate nervous system.

Keywords

Biology, Neuroscience; Health Sciences, Pharmacology

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3001171