Receptor tyrosine phosphatase-delta is a homophilic, neurite-promoting cell adhesion molecular for CNS neurons.
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. One vertebrate RPTP, PTP-delta, is highly expressed in brain and has a cell adhesion molecule-like extracellular domain (ECD) comprising three immunoglobulin repeats and eight fibronectin type III repeats. Using fluorescent beads (Covaspheres) coated with the PTP-delta ECD, as well as insect cells expressing PTP-delta on their surfaces, we show that PTP-delta is a homophilic cell adhesion molecule. A variety of chick neurons adhere strongly to an Fc fusion protein containing the PTP-delta ECD. Additionally, substrate-bound PTP-delta ECD fusion protein strongly promotes neurite outgrowth from forebrain neurons; this effect is separable from its effect on adhesion. Our results indicate that PTP-delta is a neurite-promoting cell adhesion molecule for CNS neurons.
Wang
J
J
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Florida 33101, USA.
Bixby
J L
JL
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D016466:CHO Cells; D020134:Catalytic Domain; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D003001:Cloning, Molecular; D006224:Cricetinae; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D016501:Neurites / Q000201:enzymology*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D016548:Prosencephalon / Q000166:cytology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D015816:Cell Adhesion Molecules, Neuronal; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C090899:PTPRD protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2