LAR PTP receptor: a small ectodomain isoform functions as a homophilic ligand and promotes neurite outgrowth.

YANG T, BERNABEU R, ZHANG JS, XIE Y, MASSA S, YEO TT, REMPEL H, GUM ET AND LONGO FM.

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2003 vol. 23 p. 23 - 30

0270-6474

The identities of ligands interacting with protein tyrosine phosphatase (PTP) receptors to regulate neurite outgrowth remain mainlyunknown. Analysis of cDNA and genomic clones encoding the rat leukocyte common antigen-related (LAR) PTP receptor predicted asmall,11 kDa ectodomain isoform, designated LARFN5C, containing a novel N terminal followed by a C-terminal segment of the LARfifth fibronectin type III domain. RT-PCR and Northern blot analysis confirmed the presence of LARFN5C transcripts in brain. Transfectionof COS cells with LARFN5C-FccDNAresulted in expression of the predicted protein, and Western blot analysis verified expressionof 11 kDa LARFN5C protein in vivo and its developmental regulation. Beads coated with rLARFN5C demonstrated aggregation consistentwith homophilic binding, and pull-down and immunoprecipitation assays demonstrated that rLARFN5C associates with the LARreceptor. rLARFN5C binding to COS cells was dependent on LAR expression, and rLARFN5C binding to LAR/hippocampal neuronswas fivefold greater than that found by using LAR-deficient (/) neurons. Substratum-bound rLARFN5C had potent neuritepromotingeffects on LAR/neurons, with a fivefold loss in potency with the use of LAR/neurons. rLARFN5C in solution at lownanomolar 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 promoteneurite outgrowth.