Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains

Aneesh R. Sathe, G. V. Shivashankar, Michael Sheetz

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The nuclear transport of paxillin appears to be crucial for paxillin function but the mechanism of transport remains unclear. Here, we show that the nuclear transport of paxillin is regulated by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Circular islands caused higher focal adhesion turnover and increased the nuclear transport of paxillin relative to triangular islands. Mutating several residues of paxillin had no effect on its nuclear transport, suggesting that the process is controlled by multiple domains. Knocking out FAK (also known as PTK2) and vinculin caused an increase in nuclear paxillin. This could be reversed by rescue with wild-type FAK but not by FAK with a mutated FAT domain, which inhibits paxillin binding. Expressing just the FAT domain of FAK not only brought down nuclear levels of paxillin but also caused a large immobile fraction of paxillin to be present at focal adhesions, as demonstrated by fluorescence recovery after photobleaching (FRAP) studies. Taken together, focal adhesion turnover and FAT domains regulate the nuclear localization of paxillin, suggesting a possible role for transcriptional control, through paxillin, by focal adhesions.

Original languageEnglish (US)
Pages (from-to)1981-1988
Number of pages8
JournalJournal of Cell Science
Volume129
Issue number10
DOIs
StatePublished - May 15 2016
Externally publishedYes

Fingerprint

Paxillin
Focal Adhesions
Cell Nucleus Active Transport
Islands
Fluorescence Recovery After Photobleaching
Vinculin
Fibronectins

Keywords

  • FAT domain
  • Focal adhesion
  • Nucleus
  • Paxillin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains. / Sathe, Aneesh R.; Shivashankar, G. V.; Sheetz, Michael.

In: Journal of Cell Science, Vol. 129, No. 10, 15.05.2016, p. 1981-1988.

Research output: Contribution to journalArticle

Sathe, Aneesh R. ; Shivashankar, G. V. ; Sheetz, Michael. / Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains. In: Journal of Cell Science. 2016 ; Vol. 129, No. 10. pp. 1981-1988.
@article{9b1de4cbd28e4ea7a6ec61ef3df8f4d5,
title = "Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains",
abstract = "The nuclear transport of paxillin appears to be crucial for paxillin function but the mechanism of transport remains unclear. Here, we show that the nuclear transport of paxillin is regulated by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Circular islands caused higher focal adhesion turnover and increased the nuclear transport of paxillin relative to triangular islands. Mutating several residues of paxillin had no effect on its nuclear transport, suggesting that the process is controlled by multiple domains. Knocking out FAK (also known as PTK2) and vinculin caused an increase in nuclear paxillin. This could be reversed by rescue with wild-type FAK but not by FAK with a mutated FAT domain, which inhibits paxillin binding. Expressing just the FAT domain of FAK not only brought down nuclear levels of paxillin but also caused a large immobile fraction of paxillin to be present at focal adhesions, as demonstrated by fluorescence recovery after photobleaching (FRAP) studies. Taken together, focal adhesion turnover and FAT domains regulate the nuclear localization of paxillin, suggesting a possible role for transcriptional control, through paxillin, by focal adhesions.",
keywords = "FAT domain, Focal adhesion, Nucleus, Paxillin",
author = "Sathe, {Aneesh R.} and Shivashankar, {G. V.} and Michael Sheetz",
year = "2016",
month = "5",
day = "15",
doi = "10.1242/jcs.172643",
language = "English (US)",
volume = "129",
pages = "1981--1988",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "10",

}

TY - JOUR

T1 - Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains

AU - Sathe, Aneesh R.

AU - Shivashankar, G. V.

AU - Sheetz, Michael

PY - 2016/5/15

Y1 - 2016/5/15

N2 - The nuclear transport of paxillin appears to be crucial for paxillin function but the mechanism of transport remains unclear. Here, we show that the nuclear transport of paxillin is regulated by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Circular islands caused higher focal adhesion turnover and increased the nuclear transport of paxillin relative to triangular islands. Mutating several residues of paxillin had no effect on its nuclear transport, suggesting that the process is controlled by multiple domains. Knocking out FAK (also known as PTK2) and vinculin caused an increase in nuclear paxillin. This could be reversed by rescue with wild-type FAK but not by FAK with a mutated FAT domain, which inhibits paxillin binding. Expressing just the FAT domain of FAK not only brought down nuclear levels of paxillin but also caused a large immobile fraction of paxillin to be present at focal adhesions, as demonstrated by fluorescence recovery after photobleaching (FRAP) studies. Taken together, focal adhesion turnover and FAT domains regulate the nuclear localization of paxillin, suggesting a possible role for transcriptional control, through paxillin, by focal adhesions.

AB - The nuclear transport of paxillin appears to be crucial for paxillin function but the mechanism of transport remains unclear. Here, we show that the nuclear transport of paxillin is regulated by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Circular islands caused higher focal adhesion turnover and increased the nuclear transport of paxillin relative to triangular islands. Mutating several residues of paxillin had no effect on its nuclear transport, suggesting that the process is controlled by multiple domains. Knocking out FAK (also known as PTK2) and vinculin caused an increase in nuclear paxillin. This could be reversed by rescue with wild-type FAK but not by FAK with a mutated FAT domain, which inhibits paxillin binding. Expressing just the FAT domain of FAK not only brought down nuclear levels of paxillin but also caused a large immobile fraction of paxillin to be present at focal adhesions, as demonstrated by fluorescence recovery after photobleaching (FRAP) studies. Taken together, focal adhesion turnover and FAT domains regulate the nuclear localization of paxillin, suggesting a possible role for transcriptional control, through paxillin, by focal adhesions.

KW - FAT domain

KW - Focal adhesion

KW - Nucleus

KW - Paxillin

UR - http://www.scopus.com/inward/record.url?scp=84970979595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84970979595&partnerID=8YFLogxK

U2 - 10.1242/jcs.172643

DO - 10.1242/jcs.172643

M3 - Article

C2 - 27068537

AN - SCOPUS:84970979595

VL - 129

SP - 1981

EP - 1988

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 10

ER -