Leukocyte antigen-related protein tyrosine phosphatase receptor: a small ectodomain isoform functions as a homophilic ligand and promotes neurite outgrowth.
The identities of ligands interacting with protein tyrosine phosphatase (PTP) receptors to regulate neurite outgrowth remain mainly unknown. Analysis of cDNA and genomic clones encoding the rat leukocyte common antigen-related (LAR) PTP receptor predicted a small, approximately 11 kDa ectodomain isoform, designated LARFN5C, containing a novel N terminal followed by a C-terminal segment of the LAR fifth fibronectin type III domain. RT-PCR and Northern blot analysis confirmed the presence of LARFN5C transcripts in brain. Transfection of COS cells with LARFN5C-Fc cDNA resulted in expression of the predicted protein, and Western blot analysis verified expression of approximately 11 kDa LARFN5C protein in vivo and its developmental regulation. Beads coated with rLARFN5C demonstrated aggregation consistent with homophilic binding, and pull-down and immunoprecipitation assays demonstrated that rLARFN5C associates with the LAR receptor. rLARFN5C binding to COS cells was dependent on LAR expression, and rLARFN5C binding to LAR +/+ hippocampal neurons was fivefold greater than that found by using LAR-deficient (-/-) neurons. Substratum-bound rLARFN5C had potent neurite-promoting effects on LAR +/+ neurons, with a fivefold loss in potency with the use of LAR -/- neurons. rLARFN5C in solution at low nanomolar concentrations inhibited neurite outgrowth induced by substratum-bound rLARFN5C, consistent with receptor-based function. These studies suggest that a small ectodomain isoform of a PTP receptor can function as a ligand for the same receptor to promote neurite outgrowth.
Yang
Tao
T
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Bernabeu
Ramon
R
Xie
Youmei
Y
Zhang
Julie S
JS
Massa
Stephen M
SM
Rempel
Hans C
HC
Longo
Frank M
FM
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D019556:COS Cells; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008863:Microspheres; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D008024:Ligands; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C516772:PTPRF protein, human; D017027:Protein Tyrosine Phosphatases; C000709129:Ptprf protein, mouse; C516774:Ptprf protein, rat; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2