A novel mechanism for the autonomous termination of pre-B cell receptor expression via induction of lysosome-associated protein transmembrane 5

Yohei Kawano, Rika Ouchida, Ji Yang Wang, Soichiro Yoshikawa, Mutsumi Yamamoto, Daisuke Kitamura, Hajime Karasuyama

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4462-4471
Number of pages10
JournalMolecular and Cellular Biology
Volume32
Issue number21
DOIs
Publication statusPublished - Nov 1 2012
Externally publishedYes

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Pre-B Cell Receptors
Lysosomes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

A novel mechanism for the autonomous termination of pre-B cell receptor expression via induction of lysosome-associated protein transmembrane 5. / Kawano, Yohei; Ouchida, Rika; Wang, Ji Yang; Yoshikawa, Soichiro; Yamamoto, Mutsumi; Kitamura, Daisuke; Karasuyama, Hajime.

In: Molecular and Cellular Biology, Vol. 32, No. 21, 01.11.2012, p. 4462-4471.

Research output: Contribution to journalArticle

Kawano, Yohei ; Ouchida, Rika ; Wang, Ji Yang ; Yoshikawa, Soichiro ; Yamamoto, Mutsumi ; Kitamura, Daisuke ; Karasuyama, Hajime. / A novel mechanism for the autonomous termination of pre-B cell receptor expression via induction of lysosome-associated protein transmembrane 5. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 21. pp. 4462-4471.
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