The X11L/X11beta/MINT2 and X11L2/X11gamma/MINT3 scaffold proteins shuttle between the nucleus and cytoplasm

Experimental Cell Research
Akio SumiokaToshiharu Suzuki

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...Continue Reading

References

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Citations

Jul 25, 2008·The Journal of Biological Chemistry·Toshiharu Suzuki, Tadashi Nakaya
Dec 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrzej SwistowskiDale E Bredesen
Feb 13, 2016·Analytical Biochemistry·Jack O'Sullivan, Hilary E M McMahon
Aug 25, 2015·Biochimica Et Biophysica Acta·Jack O'SullivanHilary E M McMahon
Jun 9, 2016·Brain Research·Rika MotodateToshiharu Suzuki
Jun 10, 2010·Neuroreport·Kwok-Fai LauChristopher C J Miller
Apr 21, 2017·Frontiers in Molecular Neuroscience·Suzanne GuénetteStefan Kins

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