The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP depletion

Eric D. Schwoebel, Thai H Ho, Mary Shannon Moore

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Ran-dependent nuclear transport requires a nuclear pool of RanGTP both for the assembly of export complexes and the disassembly of import complexes. Accordingly, in order for these processes to proceed, Ran-dependent nuclear import and export assays in vitro require the addition of GTP to produce RanGTP. Notably, no ATP requirement can be detected for these transport processes in vitro. But in vivo, when cells are depleted of ATP by the addition of sodium azide and 2-deoxyglucose to block ATP production by oxidative phosphorylation and glycolysis, respectively, Ran-dependent nuclear import and export are rapidly inhibited. This raised the question of whether there is an ATP requirement for these nuclear transport pathways in an intact cell that has remained undetected in vitro. Here we report that the free (but not total) GTP concentration rapidly drops to an undetectable level upon ATP depletion as does the availability of RanGTP. Our conclusion is that the inhibition of Ran-dependent nuclear transport observed upon ATP depletion in vivo results from a shortage of RanGTP rather than the inhibition of some ATP-dependent process.

Original languageEnglish (US)
Pages (from-to)963-974
Number of pages12
JournalJournal of Cell Biology
Volume157
Issue number6
DOIs
StatePublished - Jun 10 2002
Externally publishedYes

Fingerprint

Cell Nucleus Active Transport
Adenosine Triphosphate
Guanosine Triphosphate
Sodium Azide
Oxidative Phosphorylation
Deoxyglucose
Glycolysis
In Vitro Techniques

Keywords

  • ATP
  • Nuclear
  • Ran
  • Ribavirin
  • Transport

ASJC Scopus subject areas

  • Cell Biology

Cite this

The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP depletion. / Schwoebel, Eric D.; Ho, Thai H; Moore, Mary Shannon.

In: Journal of Cell Biology, Vol. 157, No. 6, 10.06.2002, p. 963-974.

Research output: Contribution to journalArticle

Schwoebel, Eric D. ; Ho, Thai H ; Moore, Mary Shannon. / The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP depletion. In: Journal of Cell Biology. 2002 ; Vol. 157, No. 6. pp. 963-974.
@article{fc229e7ddbac41e8961c84a93fecdb8e,
title = "The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP depletion",
abstract = "Ran-dependent nuclear transport requires a nuclear pool of RanGTP both for the assembly of export complexes and the disassembly of import complexes. Accordingly, in order for these processes to proceed, Ran-dependent nuclear import and export assays in vitro require the addition of GTP to produce RanGTP. Notably, no ATP requirement can be detected for these transport processes in vitro. But in vivo, when cells are depleted of ATP by the addition of sodium azide and 2-deoxyglucose to block ATP production by oxidative phosphorylation and glycolysis, respectively, Ran-dependent nuclear import and export are rapidly inhibited. This raised the question of whether there is an ATP requirement for these nuclear transport pathways in an intact cell that has remained undetected in vitro. Here we report that the free (but not total) GTP concentration rapidly drops to an undetectable level upon ATP depletion as does the availability of RanGTP. Our conclusion is that the inhibition of Ran-dependent nuclear transport observed upon ATP depletion in vivo results from a shortage of RanGTP rather than the inhibition of some ATP-dependent process.",
keywords = "ATP, Nuclear, Ran, Ribavirin, Transport",
author = "Schwoebel, {Eric D.} and Ho, {Thai H} and Moore, {Mary Shannon}",
year = "2002",
month = "6",
day = "10",
doi = "10.1083/jcb.200111077",
language = "English (US)",
volume = "157",
pages = "963--974",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP depletion

AU - Schwoebel, Eric D.

AU - Ho, Thai H

AU - Moore, Mary Shannon

PY - 2002/6/10

Y1 - 2002/6/10

N2 - Ran-dependent nuclear transport requires a nuclear pool of RanGTP both for the assembly of export complexes and the disassembly of import complexes. Accordingly, in order for these processes to proceed, Ran-dependent nuclear import and export assays in vitro require the addition of GTP to produce RanGTP. Notably, no ATP requirement can be detected for these transport processes in vitro. But in vivo, when cells are depleted of ATP by the addition of sodium azide and 2-deoxyglucose to block ATP production by oxidative phosphorylation and glycolysis, respectively, Ran-dependent nuclear import and export are rapidly inhibited. This raised the question of whether there is an ATP requirement for these nuclear transport pathways in an intact cell that has remained undetected in vitro. Here we report that the free (but not total) GTP concentration rapidly drops to an undetectable level upon ATP depletion as does the availability of RanGTP. Our conclusion is that the inhibition of Ran-dependent nuclear transport observed upon ATP depletion in vivo results from a shortage of RanGTP rather than the inhibition of some ATP-dependent process.

AB - Ran-dependent nuclear transport requires a nuclear pool of RanGTP both for the assembly of export complexes and the disassembly of import complexes. Accordingly, in order for these processes to proceed, Ran-dependent nuclear import and export assays in vitro require the addition of GTP to produce RanGTP. Notably, no ATP requirement can be detected for these transport processes in vitro. But in vivo, when cells are depleted of ATP by the addition of sodium azide and 2-deoxyglucose to block ATP production by oxidative phosphorylation and glycolysis, respectively, Ran-dependent nuclear import and export are rapidly inhibited. This raised the question of whether there is an ATP requirement for these nuclear transport pathways in an intact cell that has remained undetected in vitro. Here we report that the free (but not total) GTP concentration rapidly drops to an undetectable level upon ATP depletion as does the availability of RanGTP. Our conclusion is that the inhibition of Ran-dependent nuclear transport observed upon ATP depletion in vivo results from a shortage of RanGTP rather than the inhibition of some ATP-dependent process.

KW - ATP

KW - Nuclear

KW - Ran

KW - Ribavirin

KW - Transport

UR - http://www.scopus.com/inward/record.url?scp=0037054554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037054554&partnerID=8YFLogxK

U2 - 10.1083/jcb.200111077

DO - 10.1083/jcb.200111077

M3 - Article

C2 - 12058015

AN - SCOPUS:0037054554

VL - 157

SP - 963

EP - 974

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -