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Interactomics of the RLTPR protein explain its essential role for costimulation via CD28

ABSTRACT: The RLTPR cytosolic protein has an essential role in CD28 costimulation but its mode of action and importance in human T cells remain elusive. Here, using mass spectrometry we showed that CD28, RLTPR and the CARMA1 cytosolic adaptor physically associate in mouse T cells. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 costimulation. Our findings underpin the convergent function of RLTPR in T cells and suggest that its scaffolding role predominates during CD28 costimulation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell

SUBMITTER: Luc Camoin

LAB HEAD: Luc Camoin

PROVIDER: PXD003870 | Pride | 2016-09-27

REPOSITORIES: Pride

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The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells.

Roncagalli Romain R Cucchetti Margot M Jarmuzynski Nicolas N Grégoire Claude C Bergot Elise E Audebert Stéphane S Baudelet Emilie E Menoita Marisa Goncalves MG Joachim Anais A Durand Stéphane S Suchanek Miloslav M Fiore Frédéric F Zhang Lichen L Zhang Lichen L Liang Yinming Y Camoin Luc L Malissen Marie M Malissen Bernard B

The Journal of experimental medicine 20160919 11

The RLTPR cytosolic protein, also known as CARMIL2, is essential for CD28 co-stimulation in mice, but its importance in human T cells and mode of action remain elusive. Here, using affinity purification followed by mass spectrometry analysis, we showed that RLTPR acts as a scaffold, bridging CD28 to the CARD11/CARMA1 cytosolic adaptor and to the NF-κB signaling pathway, and identified proteins not found before within the CD28 signaling pathway. We further demonstrated that RLTPR is essential for ...[more]

PMID: 27647348

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