| First Author | Kawano Y | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 21 | Pages | 4462-71 |
| PubMed ID | 22949502 | Mgi Jnum | J:189244 |
| Mgi Id | MGI:5444793 | Doi | 10.1128/MCB.00531-12 |
| Citation | Kawano Y, et al. (2012) A Novel Mechanism for the Autonomous Termination of Pre-B Cell Receptor Expression via Induction of Lysosome-Associated Protein Transmembrane 5. Mol Cell Biol 32(21):4462-71 |
| abstractText | The expression of the pre-B cell receptor (BCR) is confined to the early stage of B cell development, and its dysregulation is associated with anomalies of B-lineage cells, including leukemogenesis. Previous studies suggested that the pre-BCR signal might trigger the autonomous termination of pre-BCR expression even before the silencing of pre-BCR gene expression to prevent sustained pre-BCR expression. However, the underlying mechanism remains ill defined. Here we demonstrate that the pre-BCR signal induces the expression of lysosome-associated protein transmembrane 5 (LAPTM5), which leads to the prompt downmodulation of the pre-BCR. While LAPTM5 induction had no significant impact on the internalization of cell surface pre-BCR, it elicited the translocation of a large pool of intracellular pre-BCR from the endoplasmic reticulum to the lysosomal compartment concomitantly with a drastic reduction of the level of intracellular pre-BCR proteins. This reduction was inhibited by lysosomal inhibitors, indicating the lysosomal degradation of the pre-BCR. Notably, the LAPTM5 deficiency in pre-B cells led to the augmented expression level of surface pre-BCR. Collectively, the pre-BCR induces the prompt downmodulation of its own expression through the induction of LAPTM5, which promotes the lysosomal transport and degradation of the intracellular pre-BCR pool and, hence, limits the supply of pre-BCR to the cell surface. |
