Identification of CMTM7 as a transmembrane linker of BLNK and the B-cell receptor.

PloS One
Atsuko MiyazakiDaisuke Kitamura

Abstract

BLNK is a pivotal adaptor protein in the signal transduction pathway from the IgM class B-cell receptor. BLNK is phosphorylated by Syk and binds various signaling intermediates, leading to cellular events including MAP-kinase activation, culminating in cellular activation. It remains unclear how BLNK is initially recruited to the surface IgM (sIgM) complex to which Syk is also recruited. Here we show that CMTM7, a tetra-spanning membrane protein of unknown function, co-localized with clathrin and sIgM at the plasma membrane. RNA-interference-mediated knockdown of CMTM7 expression in B cells resulted in an impairment of sIgM-ligation-induced tyrosine phosphorylation of BLNK, which was due to an impaired interaction of BLNK and Syk, and in a failure to activate JNK and ERK, but not upstream kinases such as Src-family kinases and Syk. CMTM7 was bound to BLNK in a membrane fraction, and their association was augmented after sIgM ligation. Exogenous CMTM7 or a mutant with an N-terminal deletion (ΔN), but not one with a C-terminal deletion (ΔC) that is defective in membrane localization, were able to restore BLNK-Syk binding, BLNK phosphorylation and ERK activation in the CMTM7-knockdown B cells. In addition, CMTM7 and the ΔN, but no...Continue Reading

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Citations

Oct 2, 2013·International Immunology·Yanfei ZhangWenling Han
Sep 26, 2013·Seminars in Cancer Biology·Carsten U Niemann, Adrian Wiestner
Aug 17, 2017·Nature·Riccardo MezzadraTon N M Schumacher
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Mar 1, 2020·International Journal of Environmental Research and Public Health·Qi ZhuYu Huan Yang
Mar 25, 2019·The Kaohsiung Journal of Medical Sciences·Zi-Ming HuangFeng Xu
May 14, 2019·International Immunology·Zhengyang LiuWenling Han

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Methods Mentioned

BETA
flow cytometry
immunoprecipitation
confocal microscopy
PCR

Software Mentioned

Science Lab 2001 Image Gauge

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