Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta isoforms.
Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a receptor-like protein tyrosine phosphatase specifically expressed in the brain. Alternative splicing produces three isoforms of this molecule: PTPzeta-A, the full-length form of PTPzeta; PTPzeta-B, the short form of PTPzeta; and PTPzeta-S, an extracellular variant. Here, we identified all these isoforms, including PTPzeta-B, as chondroitin sulfate proteoglycans, and characterized their carbohydrate modification and expression profiles in the rat brain. The level of PTPzeta-A expression was maintained during the prenatal period and decreased rapidly after birth. PTPzeta-S was expressed in a similar manner, although the postnatal decrease was gradual. In contrast, relatively constant amounts of PTPzeta-B were observed from embryonic day 13 (E13) through adulthood. PTPzeta-A and -S were constantly expressed only as proteoglycans during development, but a substantial amount of PTPzeta-B was detected in a non-proteoglycan form at E13-15. Moreover, PTPzeta-B did not contain LeX, HNK-1 carbohydrate, or keratan sulfate, although PTPzeta-A and -S were generally modified with these carbohydrates. L cells transfected with PTPzeta-A and -B cDNAs expressed these proteins as enzymatically active chondroitin sulfate proteoglycans. The PTPzeta-A and -B in L cells showed essentially similar localizations in cell cortical structures on immunofluorescence microscopy, although immature or processed forms of PTPzeta-A were accumulated additively in intracellular patchy structures. These results show that the three isoforms of PTPzeta are differentially regulated during development, and that the extracellular deleted region in PTPzeta-B is important for determination of carbohydrate modification.
Nishiwaki
T
T
Division of Molecular Neurobiology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji-cho, Okazaki 444-8585, Japan.
Maeda
N
N
Noda
M
M
D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development*; D002809:Chondroitin Sulfates / Q000737:chemistry; D018076:DNA, Complementary; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007527:Isoenzymes; D007632:Keratan Sulfate / Q000378:metabolism; D007739:L Cells; D016256:Lewis X Antigen; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D014162:Transfection
D018076:DNA, Complementary; D007527:Isoenzymes; D016256:Lewis X Antigen; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D002809:Chondroitin Sulfates; D007632:Keratan Sulfate; D017027:Protein Tyrosine Phosphatases; C516851:Ptprg protein, mouse; C516852:Ptprg protein, rat; C516896:Ptprz1 protein, mouse; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5