Abstract
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.
Publication types
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Baculoviridae / genetics
-
CHO Cells
-
Catalytic Domain
-
Cell Adhesion / physiology
-
Cell Adhesion Molecules, Neuronal / chemistry
-
Cell Adhesion Molecules, Neuronal / genetics
-
Cell Adhesion Molecules, Neuronal / metabolism
-
Chick Embryo
-
Cloning, Molecular
-
Cricetinae
-
Gene Expression Regulation, Developmental
-
Gene Expression Regulation, Enzymologic
-
Humans
-
Molecular Sequence Data
-
Neurites / enzymology*
-
Neurons / cytology*
-
Neurons / enzymology*
-
Neurons / ultrastructure
-
Prosencephalon / cytology
-
Protein Binding / physiology
-
Protein Structure, Tertiary
-
Protein Tyrosine Phosphatases / chemistry
-
Protein Tyrosine Phosphatases / genetics*
-
Protein Tyrosine Phosphatases / metabolism*
-
RNA, Messenger / analysis
-
Receptor-Like Protein Tyrosine Phosphatases, Class 2
-
Recombinant Fusion Proteins / genetics
-
Sequence Homology, Amino Acid
-
Transfection
Substances
-
Cell Adhesion Molecules, Neuronal
-
RNA, Messenger
-
Recombinant Fusion Proteins
-
PTPRD protein, human
-
Protein Tyrosine Phosphatases
-
Receptor-Like Protein Tyrosine Phosphatases, Class 2