Class B β-arrestin2-dependent CCR5 signalosome retention with natural antibodies to CCR5

Assunta Venuti, Claudia Pastori, Rosamaria Pennisi, Agostino Riva, Maria Teresa Sciortino, Lucia Lopalco

Research output: Contribution to journalArticle

Abstract

CCR5 stimulation with natural ligands, such as RANTES, classically induces short-term internalization with transient activation of β-arrestins and rapidly recycling on the cell surface. Here we discovered that, in T cells, natural CCR5 antibodies induce a CCR5-negative phenotype with the involvement of β-arrestin2, which leads to the formation of a stable CCR5 signalosome with both β-arrestin2 and ERK1. The activation of β-arrestin2 is necessary to CCR5 signaling for the signalosome formation and stabilization. When all stimuli were washed out, β-arrestin1 silencing favors the activity of β-arrestin2 for the CCR5 signalosome retention. Interestingly, CCR5 turn from Class A trafficking pattern, normally used for its internalization with natural modulating molecules (i.e. RANTES), into a long lasting Class B type specifically induced by stimulation with natural anti-CCR5 antibodies. This new CCR5 pathway is relevant not only to study in depth the molecular basis of all pathologies where CCR5 is involved but also to generate new antidody-based therapeutics.

Original languageEnglish
Article number39382
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Dec 23 2016

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Chemokine CCL5
Chemical activation
Arrestins
T-cells
Antibodies
Pathology
Recycling
Stabilization
Ligands
Molecules

ASJC Scopus subject areas

  • General

Cite this

Class B β-arrestin2-dependent CCR5 signalosome retention with natural antibodies to CCR5. / Venuti, Assunta; Pastori, Claudia; Pennisi, Rosamaria; Riva, Agostino; Sciortino, Maria Teresa; Lopalco, Lucia.

In: Scientific Reports, Vol. 6, 39382, 23.12.2016.

Research output: Contribution to journalArticle

Venuti, Assunta ; Pastori, Claudia ; Pennisi, Rosamaria ; Riva, Agostino ; Sciortino, Maria Teresa ; Lopalco, Lucia. / Class B β-arrestin2-dependent CCR5 signalosome retention with natural antibodies to CCR5. In: Scientific Reports. 2016 ; Vol. 6.
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