RT Journal Article
SR Electronic
T1 ERM-Dependent Assembly of T-Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli Prior to Activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 766196
DO 10.1101/766196
A1 Ghosh, Shirsendu
A1 Di Bartolo, Vincenzo
A1 Tubul, Liron
A1 Shimoni, Eyal
A1 Kartvelishvily, Elena
A1 Dadosh, Tali
A1 Feigelson, Sara W.
A1 Alon, Ronen
A1 Alcover, Andres
A1 Haran, Gilad
YR 2019
UL http://biorxiv.org/content/early/2019/09/12/766196.abstract
AB T-cell surfaces are covered with microvilli, actin-rich and flexible protrusions. We use super-resolution microscopy to show that ≥90% T-cell receptor (TCR) complex molecules TCRαβ and TCRζ, as well as the co-receptor CD4 and the co-stimulatory molecule CD2 reside on microvilli of human T cells. Furthermore, TCR proximal signaling molecules involved in the initial stages of the immune response, such as the protein tyrosine kinase Lck and the key adaptor molecule LAT, are also enriched on microvilli. Notably, phosphorylated proteins of the ERM (ezrin, radixin, moesin) family colocalize with these heterodimers as well as with actin filaments within the microvilli of resting T cells. This finding implies a role for one or more phosphorylated ERMs in linking the TCR complex to the actin cytoskeleton within microvilli. Indeed, expression of a dominant-negative ezrin fragment effectively redistributes TCR molecules over the whole T cell surface. Our results establish microvilli as key signaling hubs, in which the TCR complex and its proximal signaling molecules and adaptors are pre-assembled prior to activation in an ERM-dependent manner. The preformed positioning of these actin-binding TCR assemblies on individual microvilli can facilitate the local transmission of TCR signals seconds after TCR occupancy and impacts the slower subsequent events that lead to the assembly of immunological synapses.