Splice variant 3, but not 2 of receptor protein-tyrosine phosphatase sigma can mediate stimulation of insulin-secretion by alpha-latrotoxin.

Alpha-latrotoxin (alpha-LTX) binds to several cell surface receptors including receptor protein-tyrosine phosphatase sigma (RPTPsigma). Here we demonstrate that transient overexpression of the short splice variant 3 conferred alpha-LTX induced secretion to hamster insulinoma (HIT-15) cells. In contrast, the long splice variant 2 containing four additional extracellular fibronectin-III domains was inactive in secretion or in a single cell assay. Toxin-sensitive (MIN6) and toxin-insensitive (HIT-T15) insulinoma cell lines as well as PC12 cells expressed similar amounts of endogenous short RPTPsigma splice variant suggesting that this receptor does not play a role for toxin-sensitivity.