Endocytic Properties of the M-type 180-kDa Receptor for Secretory Phospholipases A
(*)
- From the Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
- § To whom correspondence should be addressed. Tel.: 33-93-95-77-00; Fax: 33-93-95-77-04; douy{at}unice.fr.
Abstract
Endocytic properties of the M-type 180-kDa receptor for secretory phospholipases A
(sPLA
) were first investigated in rabbit myocytes that express it at high levels. Internalization of the receptor was shown to
be clathrin-coated pit-mediated, rapid (k
= 0.1 min
), and ligand-independent. The signal sequence for internalization was then identified upon transient and stable expression
of various receptor constructs with mutated cytoplasmic sequences. Analysis of the internalization efficiency of the mutants
suggested that the NSYY motif encodes the major endocytic signal, with the distal tyrosine residue playing the key role. Amino
acid substitutions at the putative casein kinase II phosphorylation site of the receptor did not affect internalization. A
chimeric protein composed of the extracellular and transmembrane domains of the rabbit sPLA
receptor and of the cytoplasmic domain of the structurally homologous human macrophage mannose receptor retained the high
affinity for sPLA
and was internalization competent, exhibiting 50% endocytic activity of the M-type sPLA
receptor. The results indicate the compatibility of the structural domains of the two parent proteins and provide evidence
for the interchangeable character of their internalization signals.
Footnotes
-
↵* This work was supported by the CNRS, the Association pour la Recherche sur le Cancer, Contract 6651 and the Ministère de la Défense Nationale (Grant DRET 93/122). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- sPLA
-
secretory phospholipase A
- OS
-
toxin 1 from O. scutellatus scutellatus.
- sPLA
-
- Received August 14, 1995.
- Revision received October 31, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
