Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cell Sci. 2011 Jan 1;124(Pt 1):123-32. doi: 10.1242/jcs.073197.

Depletion of nuclear actin is a key mediator of quiescence in epithelial cells.

Author information

1
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977R225A, Berkeley, CA 94720, USA. vaspencer@lbl.gov

Abstract

Functional differentiation is orchestrated by precise growth-regulatory controls conveyed by the tissue microenvironment. Cues from laminin 111 (LN1) lower transcription and suppress mammary epithelial cell growth in culture, but how LN1 induces quiescence is unknown. Recent literature points to involvement of nuclear β-actin in transcriptional regulation. Here, we show that quiescence induced by growth factor withdrawal, or LN1 addition, rapidly decreases nuclear β-actin. LN1, but not other extracellular matrix (ECM) molecules, decreases the levels of nuclear β-actin and destabilizes RNA polymerase (RNA Pol) II and III binding to transcription sites, leading to a dramatic drop in transcription and DNA synthesis. Constitutive overexpression of globular β-actin in the nucleus reverses the effect of LN1 on transcription and RNA Pol II association and prevents the cells from becoming quiescent in the presence of LN1. The physiological relevance of our findings was verified by identifying a clear spatial separation of LN1 and β-actin in developing mammary end buds. These data indicate a novel role for nuclear β-actin in growth arrest of epithelial cells and underscore the importance of the integrity of the basement membrane in homeostasis.

PMID:
21172822
PMCID:
PMC3001411
DOI:
10.1242/jcs.073197
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center