Formin-mediated Nuclear Actin at Androgen Receptors Promotes Transcription

Overview

Journal Nature

Specialty Science

Date 2023 Mar 27

PMID 36972684

Authors

Julian Knerr

Ralf Werner

Carsten Schwan

Hong Wang

Peter Gebhardt

Helga Grotsch

Almuth Caliebe

Malte Spielmann

Paul-Martin Holterhus

Robert Grosse

Nadine C Hornig

Affiliations

Soon will be listed here.

Abstract

Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic and behavioural functions, and is involved in various conditions including androgen insensitivity syndrome and prostate cancer. Here we identified functional mutations in the formin and actin nucleator DAAM2 in patients with androgen insensitivity syndrome. DAAM2 was enriched in the nucleus, where its localization correlated with that of the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2 AR droplets ranged from 0.02 to 0.06 µm in size and associated with active RNA polymerase II. DAAM2 polymerized actin directly at the AR to promote droplet coalescence in a highly dynamic manner, and nuclear actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.

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