Building of the tetraspanin web: Distinct structural domains of CD81 function in different cellular compartments

Tsipi Shoham, Ranjani Rajapaksa, Chiung Chi Kuo, Joseph Haimovich, Shoshana Levy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


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.

Original languageEnglish
Pages (from-to)1373-1385
Number of pages13
JournalMolecular and Cellular Biology
Issue number4
StatePublished - Feb 2006


FundersFunder number
National Cancer InstituteP01CA034233
National Institute of Allergy and Infectious DiseasesR01AI045900


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