Polarized distribution of mRNAs encoding a putative LDL receptor adaptor protein, xARH (autosomal recessive hypercholesterolemia) in Xenopus oocytes

Yi Zhou, Jian Zhang, Mary Lou L King

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1249-1258
Number of pages10
JournalMechanisms of Development
Volume121
Issue number10
DOIs
StatePublished - Oct 1 2004

Fingerprint

LDL Receptors
Xenopus
Oocytes
Phosphotyrosine
Messenger RNA
Proteins
RNA
Vitellogenins
Oogenesis
Clathrin
3' Untranslated Regions
Endocytosis
Embryonic Development
Mothers
Autosomal Recessive Hypercholesterolemia
Food
Injections
Liver
Genes
vitellogenin receptor

Keywords

  • 3′UTR localization signal
  • Autosomal recessive hypercholesterolemia
  • Cellular polarity
  • RNA localization
  • Vitellogenesis
  • Xenopus oogenesis

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

Polarized distribution of mRNAs encoding a putative LDL receptor adaptor protein, xARH (autosomal recessive hypercholesterolemia) in Xenopus oocytes. / Zhou, Yi; Zhang, Jian; King, Mary Lou L.

In: Mechanisms of Development, Vol. 121, No. 10, 01.10.2004, p. 1249-1258.

Research output: Contribution to journalArticle

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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.",
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