Eph receptors play pivotal roles in the axon guidance of retinal ganglion cells (RGCs) at the optic chiasm and the establishment of the topographic retinocollicular map. We previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) is specifically involved in the control of retinotectal projections in chicks through the dephosphorylation of EphA and EphB receptors. We subsequently revealed that all the mouse R3 subfamily members (PTPRB, PTPRH, PTPRJ, and PTPRO) of the receptor protein tyrosine phosphatase (RPTP) family inhibited Eph receptors as their substrates in cultured mammalian cells. We herein investigated the functional roles of R3 RPTPs in the projection of mouse retinal axon of both sexes. Ptpro and Ptprj were expressed in mouse RGCs; however, Ptprj expression levels were markedly higher than those of Ptpro Consistent with their expression levels, Eph receptor activity was significantly enhanced in Ptprj-knock-out (Ptprj-KO) retinas. In Ptprj-KO and Ptprj/Ptpro-double-KO (DKO) mice, the number of retinal axons that projected ipsilaterally or to the contralateral eye was significantly increased. Furthermore, retinal axons in Ptprj-KO and DKO mice formed anteriorly shifted ectopic terminal zones in the superior colliculus (SC). We found that c-Abl (Abelson tyrosine kinase) was downstream of ephrin-Eph signaling for the repulsion of retinal axons at the optic chiasm and in the SC. c-Abl was identified as a novel substrate for PTPRJ and PTPRO, and the phosphorylation of c-Abl was upregulated in Ptprj-KO and DKO retinas. Thus, PTPRJ regulates retinocollicular projections in mice by controlling the activity of Eph and c-Abl kinases.SIGNIFICANCE STATEMENT Correct retinocollicular projection is a prerequisite for proper vision. Eph receptors have been implicated in retinal axon guidance at the optic chiasm and the establishment of the topographic retinocollicular map. We herein demonstrated that protein tyrosine phosphatase receptor type J (PTPRJ) regulated retinal axonal projections by controlling Eph activities. The retinas of Ptprj-knock-out (KO) and Ptpro/Ptprj double-KO mice exhibited significantly enhanced Eph activities over those in wild-type mice, and their axons showed defects in pathfinding at the chiasm and retinocollicular topographic map formation. We also revealed that c-Abl (Abelson tyrosine kinase) downstream of Eph receptors was regulated by PTPRJ. These results indicate that the regulation of the ephrin-Eph-c-Abl axis by PTPRJ plays pivotal roles in the proper central projection of retinal axons during development.
Pubmed ID: 30082414 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Phosphotyrosine
View all literature mentionsThis polyclonal targets c-Abl
View all literature mentionsThis monoclonal targets Phosphotyrosine 4G10 Platinum
View all literature mentionsThis monoclonal targets Myc Tag
View all literature mentionsThis monoclonal targets phosphorylated c-Abl
View all literature mentionsThis monoclonal targets β-Tubulin III
View all literature mentionsThis monoclonal targets TUBA3E, TUBA4A, TUBA8, TUBA3C, TUBA1C, TUBA1B, TUBA3D, TUBA1A
View all literature mentionsThis polyclonal targets EFNB2
View all literature mentionsThis polyclonal targets ephrin-A2 (L-20)
View all literature mentionsThis polyclonal targets EphA4 (A-20)
View all literature mentionsThis monoclonal targets EPH A3+A4+A5 (phospho Y779 + Y779 + Y833) antibody [EPR5684]
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsMus musculus with name STOCK Ptprotm1Shs/Rbrc from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis monoclonal targets Myc Tag
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis monoclonal targets phosphorylated c-Abl
View all literature mentionsThis polyclonal targets c-Abl
View all literature mentionsThis monoclonal targets β-Tubulin III
View all literature mentionsThis monoclonal targets TUBA3E, TUBA4A, TUBA8, TUBA3C, TUBA1C, TUBA1B, TUBA3D, TUBA1A
View all literature mentionsThis polyclonal targets EFNB2
View all literature mentionsThis polyclonal targets ephrin-A2 (L-20)
View all literature mentionsThis polyclonal targets EphA4 (A-20)
View all literature mentionsThis monoclonal targets EPH A3+A4+A5 (phospho Y779 + Y779 + Y833) antibody [EPR5684]
View all literature mentionsThis monoclonal targets Phosphotyrosine 4G10 Platinum
View all literature mentionsMus musculus with name STOCK Ptprotm1Shs/Rbrc from IMSR.
View all literature mentions