Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47-SHPS-1 system.
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.
Kusakari
Shinya
S
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
Ohnishi
Hiroshi
H
Jin
Feng-Jie
FJ
Kaneko
Yuka
Y
Murata
Takaaki
T
Murata
Yoji
Y
Okazawa
Hideki
H
Matozaki
Takashi
T
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D051928:CD47 Antigen / Q000378:metabolism*; D016466:CHO Cells; D002966:Clathrin / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D051928:CD47 Antigen; D002966:Clathrin; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; C114154:epsin; D019204:GTP-Binding Proteins; D034281:Dynamins