Limits...
Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1.

Lee BS, Alvarez X, Ishido S, Lackner AA, Jung JU - J. Exp. Med. (2000)

Bottom Line: The NH(2)-terminal region of K1 specifically interacts with the mu chains of BCR complexes, and this interaction retains BCR complexes in the endoplasmic reticulum, preventing their intracellular transport to the cell surface.Thus, KSHV K1 resembles Igalpha and Igbeta in its ability to induce signaling and to interact with mu chains of the BCR.However, unlike Igalpha and Igbeta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu chains to block the intracellular transport of BCR complexes to the cell surface.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.

ABSTRACT
The B cell antigen receptor (BCR) is a large complex that consists of a disulfide-linked tetramer of two transmembrane heavy (mu) chains and two light (lambda or kappa) chains in association with a heterodimer of Igalpha and Igbeta. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a transforming protein called K1, which has structural and functional similarity to Igalpha and Igbeta. We demonstrate that K1 downregulates the expression of BCR complexes on the surface. The NH(2)-terminal region of K1 specifically interacts with the mu chains of BCR complexes, and this interaction retains BCR complexes in the endoplasmic reticulum, preventing their intracellular transport to the cell surface. Thus, KSHV K1 resembles Igalpha and Igbeta in its ability to induce signaling and to interact with mu chains of the BCR. However, unlike Igalpha and Igbeta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu chains to block the intracellular transport of BCR complexes to the cell surface. These results demonstrate a unique feature of the K1 transforming protein, which may confer virus-infected cells with a long-term survival advantage.

Show MeSH

Related in: MedlinePlus

Maturation of BCR components. BJAB/babe (BJAB) and BJAB/K1 cells were metabolically labeled with [35S]methionine and [35S]cysteine for 30 min and chased for 1 and 4 h. Cells were lysed with 1% NP-40 buffer, and radioactively labeled lysates of BJAB/babe cells and BJAB/K1 cells were used for immunoprecipitation with an anti-μ, anti-Igα, or anti-Igβ antibody. Only the part of the gel displaying the μ chain, Igα, or Igβ is shown. The data were reproduced in three independent experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1887702&req=5

Figure 7: Maturation of BCR components. BJAB/babe (BJAB) and BJAB/K1 cells were metabolically labeled with [35S]methionine and [35S]cysteine for 30 min and chased for 1 and 4 h. Cells were lysed with 1% NP-40 buffer, and radioactively labeled lysates of BJAB/babe cells and BJAB/K1 cells were used for immunoprecipitation with an anti-μ, anti-Igα, or anti-Igβ antibody. Only the part of the gel displaying the μ chain, Igα, or Igβ is shown. The data were reproduced in three independent experiments.

Mentions: ER-localized glycoproteins bear immature N-linked glycans, which mature during intracellular transport to the medial-Golgi compartment 26. To investigate the maturation of BCR components, BJAB and BJAB/K1 cells were metabolically labeled with [35S]methionine and [35S]cysteine for 30 min, chased for 1 and 4 h, and lysed by 1% NP-40 detergent. Individual BCR components, Igα, Igβ, and μ chains, were precipitated with their specific antibodies. In addition to a 70-kD μ chain protein, a 72-kD mature form of μ chain was detected during a chase period in BJAB cells but not in BJAB/K1 cells, indicating that the μ chains of BCR underwent maturation in BJAB cells but not in BJAB/K1 cells (Fig. 7). Igα has been shown to migrate with an apparent molecular weight of 37, 40, and 43 kD 27. Unlike μ chains, no specific change of Igα and Igβ maturation was detected in K1-expressing cells (Fig. 7). These results demonstrated that K1 expression specifically blocked the maturation of the μ chains of BCR subunits.


Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1.

Lee BS, Alvarez X, Ishido S, Lackner AA, Jung JU - J. Exp. Med. (2000)

Maturation of BCR components. BJAB/babe (BJAB) and BJAB/K1 cells were metabolically labeled with [35S]methionine and [35S]cysteine for 30 min and chased for 1 and 4 h. Cells were lysed with 1% NP-40 buffer, and radioactively labeled lysates of BJAB/babe cells and BJAB/K1 cells were used for immunoprecipitation with an anti-μ, anti-Igα, or anti-Igβ antibody. Only the part of the gel displaying the μ chain, Igα, or Igβ is shown. The data were reproduced in three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887702&req=5

Figure 7: Maturation of BCR components. BJAB/babe (BJAB) and BJAB/K1 cells were metabolically labeled with [35S]methionine and [35S]cysteine for 30 min and chased for 1 and 4 h. Cells were lysed with 1% NP-40 buffer, and radioactively labeled lysates of BJAB/babe cells and BJAB/K1 cells were used for immunoprecipitation with an anti-μ, anti-Igα, or anti-Igβ antibody. Only the part of the gel displaying the μ chain, Igα, or Igβ is shown. The data were reproduced in three independent experiments.
Mentions: ER-localized glycoproteins bear immature N-linked glycans, which mature during intracellular transport to the medial-Golgi compartment 26. To investigate the maturation of BCR components, BJAB and BJAB/K1 cells were metabolically labeled with [35S]methionine and [35S]cysteine for 30 min, chased for 1 and 4 h, and lysed by 1% NP-40 detergent. Individual BCR components, Igα, Igβ, and μ chains, were precipitated with their specific antibodies. In addition to a 70-kD μ chain protein, a 72-kD mature form of μ chain was detected during a chase period in BJAB cells but not in BJAB/K1 cells, indicating that the μ chains of BCR underwent maturation in BJAB cells but not in BJAB/K1 cells (Fig. 7). Igα has been shown to migrate with an apparent molecular weight of 37, 40, and 43 kD 27. Unlike μ chains, no specific change of Igα and Igβ maturation was detected in K1-expressing cells (Fig. 7). These results demonstrated that K1 expression specifically blocked the maturation of the μ chains of BCR subunits.

Bottom Line: The NH(2)-terminal region of K1 specifically interacts with the mu chains of BCR complexes, and this interaction retains BCR complexes in the endoplasmic reticulum, preventing their intracellular transport to the cell surface.Thus, KSHV K1 resembles Igalpha and Igbeta in its ability to induce signaling and to interact with mu chains of the BCR.However, unlike Igalpha and Igbeta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu chains to block the intracellular transport of BCR complexes to the cell surface.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.

ABSTRACT
The B cell antigen receptor (BCR) is a large complex that consists of a disulfide-linked tetramer of two transmembrane heavy (mu) chains and two light (lambda or kappa) chains in association with a heterodimer of Igalpha and Igbeta. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a transforming protein called K1, which has structural and functional similarity to Igalpha and Igbeta. We demonstrate that K1 downregulates the expression of BCR complexes on the surface. The NH(2)-terminal region of K1 specifically interacts with the mu chains of BCR complexes, and this interaction retains BCR complexes in the endoplasmic reticulum, preventing their intracellular transport to the cell surface. Thus, KSHV K1 resembles Igalpha and Igbeta in its ability to induce signaling and to interact with mu chains of the BCR. However, unlike Igalpha and Igbeta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu chains to block the intracellular transport of BCR complexes to the cell surface. These results demonstrate a unique feature of the K1 transforming protein, which may confer virus-infected cells with a long-term survival advantage.

Show MeSH
Related in: MedlinePlus