Lysosomal targeting of P-selectin is mediated by a novel sequence within its cytoplasmic tail.

The Journal of Biological Chemistry
Anastasia D BlagoveshchenskayaD F Cutler

Abstract

Signals controlling the intracellular targeting of many membrane proteins are present as short sequences within their cytoplasmic domains. P-selectin is a type I membrane protein receptor for leukocytes, acting during the inflammation response. Heterologous expression experiments have demonstrated that its 35-residue cytoplasmic tail contains signals for targeting to synaptic-like microvesicles, dense-cored granules, and lysosomes. We have examined the lysosomal targeting information present within the cytoplasmic tail by site-directed mutagenesis of horseradish peroxidase-P-selectin chimeras followed by transient transfection in H.Ep.2 cells. Assaying lysosomal targeting by subcellular fractionation as well as intracellular proteolysis, we have discovered a novel lysosomal targeting signal, KCPL, located within the C1 domain of the cytoplasmic tail. Alanine substitution of this tetrapeptide reduced lysosomal targeting to the level of a tailless horseradish peroxidase-P-selectin chimera, which was previously found to be deficient in both internalization and delivery to lysosomes. A proline residue within this lysosomal targeting signal makes a major contribution to the efficiency of lysosomal targeting. A diaminobenzidine densi...Continue Reading

References

Nov 10, 1995·The Journal of Biological Chemistry·H SetiadiR P McEver
Aug 25, 1995·The Journal of Biological Chemistry·L PondP A Peterson
Aug 1, 1993·Molecular Biology of the Cell·M SubramaniamD D Wagner
Jan 1, 1993·Annual Review of Cell Biology·I S TrowbridgeC R Hopkins
May 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·W Hunziker, H J Geuze
Sep 1, 1996·The Journal of Cell Biology·J P NorcottD F Cutler
Aug 1, 1994·Trends in Cell Biology·I V Sandoval, O Bakke
Mar 1, 1997·Trends in Cell Biology·M S MarksJ S Bonracino

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Citations

Mar 17, 2005·Journal of Molecular Biology·Peter KnauthRalf Bohnensack
Dec 23, 1998·Trends in Cell Biology·W Stoorvogel
Feb 2, 2012·The Journal of Biological Chemistry·Jeroen DeclercqJohn W M Creemers
Dec 31, 2003·Molecular Biology of the Cell·Aija KyttäläJ Paul Luzio
May 4, 2004·Molecular Biology of the Cell·Ross WilliamsDaniel F Cutler
Sep 24, 2002·Seminars in Cell & Developmental Biology·Matthew J HannahDaniel F Cutler
Aug 28, 2004·Blood·Sandra L HaberichterRobert R Montgomery
Dec 10, 2003·The Journal of Cell Biology·Boris TchernychevBarbara C Furie
Jun 20, 2001·FEBS Letters·V CavalliJ Gruenberg
May 11, 2006·Traffic·Kimberly J Harrison-LavoieDaniel F Cutler
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·J-L PlantierC Négrier
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·J Gruenberg
Apr 8, 2010·Immunobiology·Anat BenadoRonit Sagi-Eisenberg
Dec 10, 2014·Cellular and Molecular Life Sciences : CMLS·Kayluz Frias BoliganStephan von Gunten
Jan 15, 2002·The Journal of Biological Chemistry·Jasber Kaur, Daniel F Cutler
Mar 30, 2001·The Journal of Biological Chemistry·J J ConkrightT E Weaver
Oct 17, 1998·The Journal of Biological Chemistry·A D BlagoveshchenskayaD F Cutler
Dec 16, 2004·The Journal of Biological Chemistry·Aija KyttäläJ Paul Luzio

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