Multiple Cos2/Ci interactions regulate Ci subcellular localization through microtubule dependent and independent mechanisms

Gelin Wang, Jin Jiang

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The Hedgehog (Hh) family of secreted proteins governs many developmental processes in both vertebrates and invertebrates. In Drosophila, Hh acts by blocking the formation of a truncated repressor form of Cubitus interruptus (Ci) and by stimulating the nuclear translocation and activity of full-length Ci (Ci155). In the absence of Hh, Ci155 is sequestered in the cytoplasm by forming protein complexes with Costal2 (Cos2), Fused (Fu) and Suppressor of Fused [Su(fu)]. How complex formation regulates Ci155 subcellular localization is not clear. We find that Cos2 interacts with two distinct domains of Ci155, an amino (N)-terminal domain (CDN) and a carboxyl (C)-terminal domain (CORD), and Cos2 competes with Su(fu) for binding to the N-terminal region of Ci155. We provide evidence that both N- and C-terminal Cos2 binding domains are involved in the cytoplasmic retention of Ci155 in imaginal discs. Treating imaginal discs with microtubule-destabilizing reagent nocodazole promotes nuclear translocation of Ci155, suggesting that the microtubule network plays an important role in the cytoplasmic retention of Ci155. In addition, we find that adding a nuclear localization signal (NLS) to exposed regions of Ci155 greatly facilitates its nuclear translocation, suggesting that the cytoplasmic retention of Ci155 may also depend on NLS masking.

Original languageEnglish (US)
Pages (from-to)493-505
Number of pages13
JournalDevelopmental Biology
Volume268
Issue number2
DOIs
StatePublished - Apr 15 2004

Keywords

  • Ci
  • Cos2
  • Hh
  • Microtubule
  • NLS
  • Nuclear translocation
  • Protein complex
  • Signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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