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First published online 18 March 2008
doi: 10.1242/jcs.025015

Journal of Cell Science 121, 1213-1223 (2008)
Published by The Company of Biologists 2008
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Research Article

Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47–SHPS-1 system

Shinya Kusakari, Hiroshi Ohnishi, Feng-Jie Jin, Yuka Kaneko, Takaaki Murata, Yoji Murata, Hideki Okazawa and Takashi Matozaki*

Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan

* Author for correspondence (e-mail: matozaki{at}showa.gunma-u.ac.jp)

Accepted 28 January 2008

CD47 and SHPS-1 are transmembrane proteins that interact with each other through their extracellular regions and constitute a bidirectional cell-cell communication system (the CD47–SHPS-1 system). We have now shown that the trans-interaction of CD47 and SHPS-1 that occurred on contact of CD47-expressing CHO cells and SHPS-1-expressing CHO cells resulted in endocytosis of the ligand-receptor complex into either cell type. Such trans-endocytosis of CD47 by SHPS-1-expressing cells was found to be mediated by clathrin and dynamin. A juxtamembrane region of SHPS-1 was indispensable for efficient trans-endocytosis of CD47, which was also regulated by Rac and Cdc42, probably through reorganization of the actin cytoskeleton. Inhibition of trans-endocytosis of CD47 promoted the aggregation of CD47-expressing cells with the cells expressing SHPS-1. Moreover, CD47 expressed on the surface of cultured mouse hippocampal neurons was shown to undergo trans-endocytosis by neighboring astrocytes expressing endogenous SHPS-1. These results suggest that trans-endocytosis of CD47 is responsible for removal of the CD47–SHPS-1 complex from the cell surface and hence regulates the function of the CD47–SHPS-1 system, at least in neurons and glial cells.

Key words: Cell-cell interaction, Clathrin, Dynamin, Small GTP-binding protein, Neuron


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