The X11L/X11β/MINT2 and X11L2/X11γ/MINT3 scaffold proteins shuttle between the nucleus and cytoplasm

Akio Sumioka, Yuhki Saito, Megumi Sakuma, Yoichi Araki, Tohru Yamamoto, Toshiharu Suzuki

Research output: Contribution to journalArticle

Abstract

The X11/MINT family proteins are adaptor scaffolding proteins involved in formation of multiprotein complexes, and trafficking and metabolism of membrane proteins such as the beta-amyloid precursor protein. We found that a significant portion of X11L and X11L2 are recovered in nuclear fraction of mouse brain homogenates. EGFP-X11s were not detected in the nucleus of N2a neuroblastoma cells; however, administration of leptomycin B (LMB) induced substantial nuclear accumulation of EGFP-X11L and EGFP-X11L2, while EGFP-X11 showed little accumulation. Fluorescence loss in photobleaching (FLIP) analysis indicated that EGFP-X11L2 and EGFP-X11L are shuttled between the cytoplasm and nucleus, the former more effectively than the latter. We identified a nuclear export signal (NES) in the N-terminus of X11L2, mutation of which induces nuclear accumulation of EGFP-X11L2 in the absence of LMB. X11L2 fused to the Gal4 DNA binding domain (DBD) showed transcriptional activity, suggesting that X11L2 could function as a transcriptional activator if tethered near a promoter. Interestingly, attenuation of the nucleo-cytoplasmic shuttling of GAL4-DBD-X11L2 by mutating the NES or attaching the SV40 nuclear localization signal significantly decreased the apparent transcriptional activity. Our observations suggest that X11L2 functions in the nucleus by a mechanism distinct from conventional transactivators.

Original languageEnglish (US)
Pages (from-to)1155-1162
Number of pages8
JournalExperimental cell research
Volume314
Issue number5
DOIs
StatePublished - Mar 10 2008
Externally publishedYes

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Keywords

  • MINT1
  • MINT2
  • MINT3
  • Nuclear export
  • Nuclear localization
  • Nucleo-cytoplasmic shuttling
  • X11
  • X11L
  • X11L2

ASJC Scopus subject areas

  • Cell Biology

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