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

Mol Cell Biol. 2006 Feb;26(4):1373-85. doi: 10.1128/MCB.26.4.1373-1385.2006.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, CD19 / chemistry
  • Antigens, CD19 / genetics
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Compartmentation
  • Cell Line
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kinetics
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Models, Molecular
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Tetraspanin 28


  • Antigens, CD
  • Antigens, CD19
  • CD81 protein, human
  • Cd81 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Tetraspanin 28