In mammals, the closely related protein tyrosine phosphatase-like type 1 transmembrane proteins ICA512 and phogrin are restricted to neuroendocrine tissues including brain, pituitary and pancreatic beta-cells, where they are localized to dense core vesicles (DCVs) of the regulated secretory pathway. Both are of clinical relevance as they represent major autoantigens in type 1 diabetes. Their physiological role remains enigmatic, though strong evolutionary conservation and functional studies suggest a conserved regulatory role in hormone and neuropeptide secretion. IDA-1 is the single C. elegans ortholog of ICA512 and phogrin and is also expressed in a subset of neurons and the neuroendocrine-like
uv1 cells in worms, suggesting functional conservation (Zahn et al., J Comp Neurol 429:127). Anti-IDA-1 immunostaining and immuno-electron microscopy show that IDA-1 is localized intracellularly to small punctate organelles identified as DCVs. The C. elegans Gene Knockout Consortium recently made available two deletion alleles within the
ida-1 locus,
tm334 and
ok409.
tm334 is a small deletion within the N-terminus of the protein, while
ok409 represents a larger deletion.
ok409 but not
tm334 animals are moderately egg-laying defective, consistent with a function for
ida-1 in the neuropeptidergic control of egg-laying. We are currently characterizing the phenotypes of these deletion mutants. The C. elegans model will aid in elucidating the physiological role of
ida-1 and its mammalian orthologs.