Lunatic fringe protein processing by proprotein convertases may contribute to the short protein half-life in the segmentation clock

Biochimica Et Biophysica Acta
Emily T Shifley, Susan E Cole

Abstract

During vertebrate segmentation, oscillatory activation of Notch signaling is important in the clock that regulates the timing of somitogenesis. In mice, the cyclic activation of NOTCH1 requires the periodic expression of Lunatic fringe (Lfng). For LFNG to play a role in the segmentation clock, its cyclic transcription must be coupled with post-translational mechanisms that confer a short protein half-life. LFNG protein is cleaved and released into the extracellular space, and here we examine the hypothesis that this secretion contributes to a short LFNG intracellular half-life, facilitating rapid oscillations within the segmentation clock. We localize N-terminal protein sequences that control the secretory behavior of fringe proteins and find that LFNG processing is promoted by specific proprotein convertases including furin and SPC6. Mutations that alter LFNG processing increase its intracellular half-life without preventing its secretion. These mutations do not affect the specificity of LFNG function in the Notch pathway, thus regulation of protein half-life affects the duration of LFNG activity without altering its function. Finally, the embryonic expression pattern of Spc6 suggests a role in terminating LFNG activity during...Continue Reading

References

Mar 24, 1995·Cell·C E LindsellG Weinmaster
May 23, 1997·The Journal of Biological Chemistry·S K Cho, R D Cummings
Jun 26, 1997·Nature·V M PaninK D Irvine
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·F JeanG Thomas
Jan 13, 1999·The Journal of Cell Biology·D B Constam, E J Robertson
Aug 10, 2000·Nature·D J MoloneyT F Vogt
Feb 13, 2001·Brain Research. Molecular Brain Research·T MikamiN Itoh
Jul 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Neil A TaylorJohn W M Creemers
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Gerry Weinmaster, Chris Kintner
Dec 31, 2003·Developmental Biology·Padmashree C G RidaYun Jin Jiang
Jun 1, 2004·Nature Genetics·Hiromi HirataRyoichiro Kageyama
Jun 24, 2004·The Journal of Membrane Biology·W W Young
Dec 3, 2004·Molecular Biology of the Cell·Liang-Tung YangGerry Weinmaster
Dec 16, 2005·Molecular and Cellular Biology·Rachid EssalmaniAnnik Prat
Apr 6, 2007·Endocrine Reviews·Victoria BolósJosé Luis de la Pompa
Jun 30, 2007·Birth Defects Research. Part C, Embryo Today : Reviews·Emily T Shifley, Susan E Cole
Oct 10, 2007·The Journal of Biological Chemistry·Aiguo XuKenneth D Irvine
Oct 30, 2007·Current Opinion in Structural Biology·Pamela Stanley
Apr 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Rachid EssalmaniAnnik Prat

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Citations

Sep 23, 2011·The Journal of Biological Chemistry·Katrine Ter-Borch Gram SchjoldagerHenrik Clausen
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Pamela Stanley
Jul 5, 2012·PLoS Computational Biology·Hendrik B TiedemannMartin Hrabě de Angelis
Jan 8, 2014·Molecular Neurobiology·Ting LiZhiping Hu
Feb 25, 2009·Journal of Theoretical Biology·Aitor González, Ryoichiro Kageyama
Oct 28, 2008·The International Journal of Biochemistry & Cell Biology·Kelvin B Luther, Robert S Haltiwanger
May 30, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jennifer L MoranSusan E Cole
Apr 10, 2018·ELife·Preetish Kadur Lakshminarasimha MurthyXiling Shen
Jul 23, 2019·FEBS Letters·Prathyush PothukuchiSeetharaman Parashuraman
Jul 16, 2017·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Kanu WahiSusan E Cole
Oct 23, 2020·Nature Reviews. Molecular Cell Biology·Katrine T SchjoldagerHenrik Clausen
Oct 4, 2020·Biochemical and Biophysical Research Communications·Takashi TsuchiyaKazuki Sasaki

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