Relationships between EGFR signaling-competent and endocytosis-competent membrane microdomains.

Claudia Puri, Daniela Tosoni, Riccardo Comai, Andrea Rabellino, Daniela Segat, Federico Caneva, Paola Luzzi, Pier Paolo Di Fiore, Carlo Tacchetti

Journal: Molecular biology of the cell 2005;16(6):2704-18

PMID: 15772153

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Abstract

Membrane microdomains, the so-called lipid rafts, function as platforms to concentrate receptors and assemble the signal transduction machinery. Internalization, in most cases, is carried out by different specialized structures, the clathrin-coated pits. Here, we show that several endocytic proteins are efficiently recruited to morphologically identified plasma membrane lipid rafts, upon activation of the epidermal growth factor (EGF) receptor (EGFR), a receptor tyrosine kinase. Analysis of detergent-resistant membrane fractions revealed that the EGF-dependent association of endocytic proteins with rafts is as efficient as that of signaling effector molecules, such as Grb2 or Shc. Finally, the EGFR, but not the nonsignaling transferrin receptor, could be localized in nascent coated pits that almost invariably contained raft membranes. Thus, specialized membrane microdomains have the ability to assemble both the molecular machineries necessary for intracellular propagation of EGFR effector signals and for receptor internalization.

Address: MicroScoBio Research Center, Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.

DOI: 10.1091/mbc.e04-07-0596