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

Abstract

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.

Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients

“…5 Nonetheless, the clinical impact of CD19 assessment may be somehow hampered by the low frequency (4%) of CD19 þ MM cases. 5 The regulatory role of tetraspanin CD81 over CD19 has been elegantly demonstrated in CD81-knockout mice; 34 --36 moreover, the N-terminus and the first transmembrane regions of CD81 are also required for normal CD19 expression, 37 and more recently van Zelm et al 12 described the first antibody deficiency syndrome caused by a mutation in the CD81 gene and consequent disruption of the CD19 complex on B cells.…”

Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK

“…A20, a B-cell lymphoma line, and CT26 colon carcinoma line were obtained from ATCC; 4T1-Luc breast carcinoma cell line was a gift from the S. Strober laboratory and the C. Contag laboratory (both at Stanford University). The H11 pre-B-cell line was generated from a C57BL/6 mouse as described (27) 2F3-leukemia cell line was generated from a BALB/c mouse as described (28). Tumor cells were cultured in complete medium (RPMI 1640; Cellgro) containing 10% (vol/vol) FBS (HyClone), 100 U/mL penicillin, 100 μg/mL streptomycin, and 50 μM 2-ME (Gibco).…”

Association of tetraspanin CD9 with transmembrane TGFα confers alterations in cell-surface presentation of TGFα and cytoskeletal organization

“…The tetraspanin CD81 facilitates the processing and transport of the glycoprotein CD19, starting with its requirement for exit from the endoplasmic reticulum to the processing and glycosylation of CD19 (Shoham et al, 2006). The tetraspanins uroplakin Ia and uroplakin Ib allow transit of the nontetraspanin uroplakins UPII and UPIII from the Golgi to the cell surface to form urothelial plaques (Tu et al, 2006).…”