Scientific article

Clathrin-coated pit-mediated receptor internalization. Role of internalization signals and receptor mobility

Published inThe Journal of biological chemistry, vol. 268, no. 31, p. 23191-23196
Publication date1993

Most signals controlling receptor-mediated endocytosis have been identified by alteration of sequences present in receptors normally internalized via clathrin-coated pits. In the present work we have reconsidered the factors that control internalization the other way around: i.e. by introducing potential internalization sequences in complement receptor 1 (CR1) which does not preferentially associate with clathrin-coated pits. The analysis of the internalization efficiency of NPxY related motifs generated by substituting His2010 and/or Glu2015 by either Phe or Tyr indicates that FxNPxY is the stronger promoter of endocytosis and that the signal efficiency depends on the presence of aromatic residues (including a tyrosine) at both ends of the -xNPx- motif. Moreover, CR1-tyr (substitution of Glu2015 for Tyr) internalization was superposable to that of a receptor composed of the extracellular and transmembrane domains of CR1 fused to the intracytoplasmic tail of the low density lipoprotein (LDL) receptor (including the FxNPxY motif) (CR1-LDL). When analyzed by fluorescence recovery after photobleaching, the surface mobility of CR1-LDL was decreased as compared with that of either CR1-tyr or CR1-wt, despite a similar association with clathrin-coated pits. The role of receptor mobility in internalization was confirmed by the observation that CR1-tl, with a deletion of the cytoplasmic tail, was more mobile and more efficiently internalized than CR1-wt.

  • Amino Acid Sequence
  • Base Sequence
  • Coated Pits, Cell-Membrane/ physiology
  • DNA Primers/chemistry
  • Endocytosis
  • Humans
  • Membrane Fluidity
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Receptors, Complement 3b/ metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
Citation (ISO format)
PACCAUD, Jean-Pierre et al. Clathrin-coated pit-mediated receptor internalization. Role of internalization signals and receptor mobility. In: The Journal of biological chemistry, 1993, vol. 268, n° 31, p. 23191–23196.
Main files (1)
ISSN of the journal0021-9258

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