CRYP-2 - A RECEPTOR-TYPE TYROSINE PHOSPHATASE SELECTIVELY EXPRESSED BY DEVELOPING VERTEBRATE NEURONS

Axonal growth and guidance, like other aspects of neuronal differentia tion, can be regulated by changes in tyrosine phosphorylation. Althoug h much is known concerning the role of tyrosine kinases in these proce sses, relatively little is known about the nature and function of prot ein tyrosine phosphatases (PTPs) that may be involved. To identify the PTPs expressed in the embryonic chicken CNS at the time of axon growt h, we performed a polymerase chain reaction based ''screen'' using deg enerate primers directed against conserved regions of the PTP catalyti c domain. We obtained five distinct PTP-related cDNAs, two of which co de for novel PTPs. One, designated CRYP-2, is selectively expressed in the CNS. Full-length cloning of CRYP-2 revealed that it is a receptor -type PTP with an adhesion molecule-like extracellular region comprisi ng fibronectin (FN) type III repeats and a single catalytic domain in the intracellular region. It is alternatively spliced in the juxtamemb rane region, similar to other PTPs recently cloned. CRYP-2 mRNA is str ongly expressed in the brain during the time of axon growth; it is dow nregulated toward the end of embryogenesis. Western blot analysis iden tifies a 330-kDa glycoprotein as CRYP-2 and confirms that the protein is downregulated after hatching. Immunostaining of cerebellar neurons in vitro reveals that CRYP-2 is expressed on neuronal cell bodies and processes, but not on glia. The CAM-like structure, developmental patt ern of expression, and neuron-specific localization of the CRYP-2 PTP suggest that it is involved in neuronal differentiation, particularly axon growth. (C) 1996 John Wiley & Sons Inc.