Abstract
The
Xenopus homologue of
hARH (human autosomal recessive hypercholesterolemia) was identified in a screen for vegetally localized RNAs.
xARH contains a N-terminal phosphotyrosine binding (PTB) domain that is 91% identical to that of the human gene, a domain previously shown to bind the LDL receptor family members. Maternal
xARH, unlike
hARH, is present as two transcripts that differ in their 3′ UTRs. The large transcript,
xARH-
α, primarily localizes to the oocyte vegetal cortex. The small transcript,
xARH-
β, is not localized. During embryogenesis,
xARH RNA is found redistributed in a perinuclear pattern. Similar to
hARH,
xARH is found in the adult liver, but at low levels compared to oocytes. Downstream of the PTB domain is a conserved clathrin box and a C terminal region 50% identical to that of hARH. Previous in vitro studies from this lab have shown xARH can bind the LDLR as well as the vitellogenin (VTG) receptor. We find that injection of the C terminal region missing the PTB domain significantly reduces the internalization of VTG in early stage oocytes, an event that requires the VTG receptor. The data strongly suggest that
xARH encodes an adaptor protein that functions in the essential receptor-mediated endocytosis of nutrients during oogenesis. Because xARH protein is found uniformly distributed along the animal/vegetal axis in oocytes, we propose that the localization of
xARH-α to the vegetal cortex while
xARH-β remains unlocalized, facilitates the uniform distribution of the protein in this extraordinarily large cell.
