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Molecular and Cellular Biology, February 2006, p. 1373-1385, Vol. 26, No. 4
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.4.1373-1385.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments{dagger}

Tsipi Shoham,1 Ranjani Rajapaksa,1 Chiung-Chi Kuo,1 Joseph Haimovich,1,2 and Shoshana Levy1*

Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, California,1 Department of Human Microbiology, Tel Aviv University Medical School, Tel Aviv, Israel2

Received 10 September 2005/ Returned for modification 26 October 2005/ Accepted 15 November 2005

The tetraspanin web is composed of a network of tetraspanins and their partner proteins that facilitate cellular interactions and fusion events by an unknown mechanism. Our aim was to unravel the web partnership between the tetraspanin CD81 and CD19, a cell surface signaling molecule in B lymphocytes. We found that CD81 plays multiple roles in the processing, intracellular trafficking, and membrane functions of CD19. Surprisingly, these different roles are embodied in distinct CD81 domains, which function in the different cellular compartments: the N-terminal tail of CD81 has an effect on the glycosylation of CD19; the first transmembrane domain of CD81 is sufficient to support the exit of CD19 from the endoplasmic reticulum, although the large extracellular loop (LEL) of CD81 associates physically with CD19 early during biosynthesis; and finally, the TM2 and TM3 domains of CD81 play a role in the transmission of signals initiated upon engagement of the LEL. The participation of distinct CD81 domains in varied functions may explain the pleiotropic effects of CD81 within the tetraspanin web.

* Corresponding author. Mailing address: Department of Medicine, Division of Oncology, CCSR Room 1105a, 269 Campus Drive, Stanford University Medical Center, Stanford, CA 94305-5151. Phone: (650) 725-6425. Fax: (650) 736-1454. E-mail: levy{at}cmgm.stanford.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, February 2006, p. 1373-1385, Vol. 26, No. 4
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.4.1373-1385.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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