Regulated expression during development and following sciatic nerve injury of mRNAs encoding the receptor tyrosine phosphatase HPTPζ/RPTPβ

Three major isoforms of the receptor protein tyrosine phosphatase HPTPζ/RPTPβ (RPTPζ/β) have been previously identified, two with identical transmembrane and intracellular catalytic domains that differ by virtue of a long cysteine-free extracellular region, and a soluble proteoglycan called phosphacan that lacks the transmembrane and carboxy-terminal catalytic domains. To determine whether these RPTPζ/β variants are produced by alternative mRNA splicing of a common primary transcript, we performed genomic Southern analysis and characterized several rat cDNA and genomic RPTPζ/β clones. These studies indicated that the three major transcripts which encode phosphacan and the two RPTPζ/β phosphatase variants are encoded by a single gene, and further that additional alternative mRNA splicing is likely to result in the deletion of a 7 amino acid insert from the intracellular juxtamembrane region of both long and short phosphatase isoforms. Simultaneous quantitation of the three major isoforms by RNase protection analysis indicated that the mRNA encoding phosphacan had the highest relative abundance in the CNS while that encoding the short phosphatase isoform was most abundant relative to the other RPTPζ/β variants in the PNS. Following peripheral nerve crush, all RPTPζ/β mRNAs, including phosphacan and the phosphatase variants with and without the 21 base insert, were significantly induced in the distal segments of the sciatic nerve with a time course that correlated well with the response of Schwann cells to this injury.