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

Paccaud, Jean-Pierre; Reith, Walter; Johansson, B.; Magnusson, K. E.; Mach, Bernard; Carpentier, J. L.

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Title		Clathrin-coated pit-mediated receptor internalization. Role of internalization signals and receptor mobility
Authors		Paccaud, Jean-Pierre Reith, Walter Johansson, B. Magnusson, K. E. Mach, Bernard Carpentier, J. L.
Published in		Journal of Biological Chemistry. 1993, vol. 268, no. 31, p. 23191-23196
Abstract		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.
Keywords		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
Identifiers		PMID: 8226838
Full text		Article - Limited access to UNIGE Other version: http://www.jbc.org/content/268/31/23191.full.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Citation (ISO format)		PACCAUD, Jean-Pierre et al. Clathrin-coated pit-mediated receptor internalization. Role of internalization signals and receptor mobility. In: Journal of Biological Chemistry, 1993, vol. 268, n° 31, p. 23191-23196. https://archive-ouverte.unige.ch/unige:11503