ERM-Dependent Assembly of T Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli prior to Activation

Shirsendu Ghosh; Vincenzo Di Bartolo; Liron Tubul; Eyal Shimoni; Elena Kartvelishvily; Tali Dadosh; Sara W. Feigelson; Ronen Alon; Andres Alcover; Gilad Haran

doi:10.1016/j.celrep.2020.02.069

ERM-Dependent Assembly of T Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli prior to Activation

Shirsendu Ghosh^*, Vincenzo Di Bartolo, Liron Tubul, Eyal Shimoni, Elena Kartvelishvily, Tali Dadosh, Sara W. Feigelson, Ronen Alon, Andres Alcover, Gilad Haran^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

T cell surfaces are covered with microvilli, actin-rich and flexible protrusions. We use super-resolution microscopy to show that ≥90% of T cell receptor (TCR) complex molecules TCRαβ and TCRζ, as well as the co-receptor CD4 (cluster of differentiation 4) and the co-stimulatory molecule CD2, reside on microvilli of resting human T cells. Furthermore, TCR proximal signaling molecules involved in the initial stages of the immune response, including the protein tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase) and the key adaptor LAT (linker for activation of T cells), are also enriched on microvilli. Notably, phosphorylated proteins of the ERM (ezrin, radixin, and moesin) family colocalize with TCRαβ as well as with actin filaments, implying a role for one or more ERMs in linking the TCR complex to the actin cytoskeleton within microvilli. Our results establish microvilli as key signaling hubs, in which the TCR complex and its proximal signaling molecules and adaptors are preassembled prior to activation in an ERM-dependent manner, facilitating initial antigen sensing.

Original language	English
Article number	766196
Pages (from-to)	3434-3447
Number of pages	14
Journal	Cell Reports
Volume	30
Issue number	10
DOIs	https://doi.org/10.1016/j.celrep.2020.02.069
Publication status	Published - 10 Mar 2020

Funding

We thank Drs. Sandeep Yadav, Alexander Vaskevich and Yunmin Jung, as well as Mr. Francesco Roncato of the Weizmann Institute of Science for their kind advice and experimental help during the project. We also thank Dr. Keir Neuman (NIH) for kindly sharing with us fluorescent nanodiamond samples. The SEM studies were conducted at the Electron Microscopy Unit of the Weizmann Institute of Science. G.H. is the incumbent of the Hilda Pomeraniec Memorial Professorial Chair. Author Contributions S.G., A.A., R.A., and G.H. designed research; S.G., V.D.B., L.T., E.S., E.K., T.D., and S.W.F. performed research; S.G. and G.H. analyzed data; and S.G., A.A., R.A., and G.H. wrote the paper.

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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https://www.biorxiv.org/content/10.1101/766196v1Licence: Other

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@article{de5657fde15d4f8ea27c64c9cbc7876e,

title = "ERM-Dependent Assembly of T Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli prior to Activation",

abstract = "T cell surfaces are covered with microvilli, actin-rich and flexible protrusions. We use super-resolution microscopy to show that ≥90% of T cell receptor (TCR) complex molecules TCRαβ and TCRζ, as well as the co-receptor CD4 (cluster of differentiation 4) and the co-stimulatory molecule CD2, reside on microvilli of resting human T cells. Furthermore, TCR proximal signaling molecules involved in the initial stages of the immune response, including the protein tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase) and the key adaptor LAT (linker for activation of T cells), are also enriched on microvilli. Notably, phosphorylated proteins of the ERM (ezrin, radixin, and moesin) family colocalize with TCRαβ as well as with actin filaments, implying a role for one or more ERMs in linking the TCR complex to the actin cytoskeleton within microvilli. Our results establish microvilli as key signaling hubs, in which the TCR complex and its proximal signaling molecules and adaptors are preassembled prior to activation in an ERM-dependent manner, facilitating initial antigen sensing.",

author = "Shirsendu Ghosh and {Di Bartolo}, Vincenzo and Liron Tubul and Eyal Shimoni and Elena Kartvelishvily and Tali Dadosh and Feigelson, {Sara W.} and Ronen Alon and Andres Alcover and Gilad Haran",

year = "2020",

month = mar,

day = "10",

doi = "10.1016/j.celrep.2020.02.069",

language = "English",

volume = "30",

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journal = "Cell Reports",

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T1 - ERM-Dependent Assembly of T Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli prior to Activation

AU - Ghosh, Shirsendu

AU - Di Bartolo, Vincenzo

AU - Tubul, Liron

AU - Shimoni, Eyal

AU - Kartvelishvily, Elena

AU - Dadosh, Tali

AU - Feigelson, Sara W.

AU - Alon, Ronen

AU - Alcover, Andres

AU - Haran, Gilad

PY - 2020/3/10

Y1 - 2020/3/10

N2 - T cell surfaces are covered with microvilli, actin-rich and flexible protrusions. We use super-resolution microscopy to show that ≥90% of T cell receptor (TCR) complex molecules TCRαβ and TCRζ, as well as the co-receptor CD4 (cluster of differentiation 4) and the co-stimulatory molecule CD2, reside on microvilli of resting human T cells. Furthermore, TCR proximal signaling molecules involved in the initial stages of the immune response, including the protein tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase) and the key adaptor LAT (linker for activation of T cells), are also enriched on microvilli. Notably, phosphorylated proteins of the ERM (ezrin, radixin, and moesin) family colocalize with TCRαβ as well as with actin filaments, implying a role for one or more ERMs in linking the TCR complex to the actin cytoskeleton within microvilli. Our results establish microvilli as key signaling hubs, in which the TCR complex and its proximal signaling molecules and adaptors are preassembled prior to activation in an ERM-dependent manner, facilitating initial antigen sensing.

AB - T cell surfaces are covered with microvilli, actin-rich and flexible protrusions. We use super-resolution microscopy to show that ≥90% of T cell receptor (TCR) complex molecules TCRαβ and TCRζ, as well as the co-receptor CD4 (cluster of differentiation 4) and the co-stimulatory molecule CD2, reside on microvilli of resting human T cells. Furthermore, TCR proximal signaling molecules involved in the initial stages of the immune response, including the protein tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase) and the key adaptor LAT (linker for activation of T cells), are also enriched on microvilli. Notably, phosphorylated proteins of the ERM (ezrin, radixin, and moesin) family colocalize with TCRαβ as well as with actin filaments, implying a role for one or more ERMs in linking the TCR complex to the actin cytoskeleton within microvilli. Our results establish microvilli as key signaling hubs, in which the TCR complex and its proximal signaling molecules and adaptors are preassembled prior to activation in an ERM-dependent manner, facilitating initial antigen sensing.

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DO - 10.1016/j.celrep.2020.02.069

M3 - Article

AN - SCOPUS:85081240516

SN - 2211-1247

VL - 30

SP - 3434

EP - 3447

JO - Cell Reports

JF - Cell Reports

IS - 10

M1 - 766196

ER -

ERM-Dependent Assembly of T Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli prior to Activation

Abstract

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All Science Journal Classification (ASJC) codes

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