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Title: Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis
Authors: Reekmans, Sara *
Pflanzner, Thorsten *
Gordts, Philip *
Isbert, Simone
Zimmermann, Pascale
Annaert, Wim
Weggen, Sascha
Roebroek, Anton ×
Pietrzik, Claus #
Issue Date: Jan-2010
Publisher: Birkhäuser Verlag
Series Title: Cellular and Molecular Life Sciences vol:67 issue:1 pages:135-145
Abstract: The proximal NPXY and distal NPXYXXL motifs in the intracellular domain of LRP1 play an important role in regulation of the function of the receptor. The impact of single and double inactivating knock-in mutations of these motifs on receptor maturation, cell surface expression, and ligand internalization was analyzed in mutant and control wild-type mice and MEFs. Single inactivation of the proximal NPXY or in combination with inactivation of the distal NPXYXXL motif are both shown to be associated with an impaired maturation and premature proteasomal degradation of full-length LRP1. Therefore, only a small mature LRP1 pool is able to reach the cell surface resulting indirectly in severe impairment of ligand internalization. Single inactivation of the NPXYXXL motif revealed normal maturation, but direct impairment of ligand internalization. In conclusion, the proximal NPXY motif proves to be essential for early steps in the LRP1 biosynthesis, whereas NPXYXXL appears rather relevant for internalization.
ISSN: 1420-682X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Molecular Genetics Section (-)
Laboratory for Experimental Mouse Genetics
Laboratory of Glycobiology and Developmental Genetics (-)
* (joint) first author
× corresponding author
# (joint) last author

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