Effects of microcystin‐lr on actin and the actin‐associated proteins α‐actinin and talin in hepatocytes

Sushmita Ghosh, Safdar All Khan, Mark Wickstrom, Val Richard Beasley

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Abstract

Microcystin‐LR (MCLR) is a commonly encountered blue‐green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments, microtubules, and actin microfilaments (MFs) in affected cells. In this study, the effect of MCLR on the sequence of alterations in MFs and actin‐associated proteins (AAPs) of isolated hepatocytes was examined in an effort to determine whether morphologic changes induced in MFs by microcystins are a result of prior dislocation of AAPs. We studied the effects of MCLR exposure on α‐actinin and talin, two AAPs that play a role in the orientation of the MFs. Primary hepatocytes were incubated with 10 μM MCLR for 0‐64 min. The distribution of actin, α‐actinin, and talin were examined using fluorescence microscopy. MCLR induced similar changes in the distribution of actin and the AAPs. Actin filament redistribution was first observed after 12 min of MCLR exposure, and was characterized by detachment of MFs from the cell periphery, followed by condensation at distinct focal points and progressive collapse into the interior of affected cells. Changes in α‐actinin and talin distribution were first observed after 20 min of toxin exposure. The AAPs appeared to detach from focal contacts on the cytoplasmic surface of the plasma membrane, condense into cytoplasmic aggregates, and ultimately collapse into a juxtanuclear bundle. The results of this study indicate that, in hepatocytes exposed to MCLR, the collapse of actin MFs occurs prior to the dislocation of α‐actinin and talin. Changes in these actin associated proteins are not likely to account for the initial changes in actin MFs. © 1995 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)405-414
Number of pages10
JournalNatural Toxins
Volume3
Issue number6
DOIs
StatePublished - Jan 1 1995

Fingerprint

Talin
Actinin
Actin Cytoskeleton
Actins
Hepatocytes
Proteins
Microcystins
Protein Phosphatase 1
Protein Phosphatase 2
Microfilament Proteins
Focal Adhesions
Intermediate Filaments
Fluorescence microscopy
Cell membranes
Fluorescence Microscopy
Microtubules
Condensation
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Ghosh, Sushmita ; Khan, Safdar All ; Wickstrom, Mark ; Beasley, Val Richard. / Effects of microcystin‐lr on actin and the actin‐associated proteins α‐actinin and talin in hepatocytes. In: Natural Toxins. 1995 ; Vol. 3, No. 6. pp. 405-414.
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Effects of microcystin‐lr on actin and the actin‐associated proteins α‐actinin and talin in hepatocytes. / Ghosh, Sushmita; Khan, Safdar All; Wickstrom, Mark; Beasley, Val Richard.

In: Natural Toxins, Vol. 3, No. 6, 01.01.1995, p. 405-414.

Research output: Contribution to journalArticle

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T1 - Effects of microcystin‐lr on actin and the actin‐associated proteins α‐actinin and talin in hepatocytes

AU - Ghosh, Sushmita

AU - Khan, Safdar All

AU - Wickstrom, Mark

AU - Beasley, Val Richard

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N2 - Microcystin‐LR (MCLR) is a commonly encountered blue‐green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments, microtubules, and actin microfilaments (MFs) in affected cells. In this study, the effect of MCLR on the sequence of alterations in MFs and actin‐associated proteins (AAPs) of isolated hepatocytes was examined in an effort to determine whether morphologic changes induced in MFs by microcystins are a result of prior dislocation of AAPs. We studied the effects of MCLR exposure on α‐actinin and talin, two AAPs that play a role in the orientation of the MFs. Primary hepatocytes were incubated with 10 μM MCLR for 0‐64 min. The distribution of actin, α‐actinin, and talin were examined using fluorescence microscopy. MCLR induced similar changes in the distribution of actin and the AAPs. Actin filament redistribution was first observed after 12 min of MCLR exposure, and was characterized by detachment of MFs from the cell periphery, followed by condensation at distinct focal points and progressive collapse into the interior of affected cells. Changes in α‐actinin and talin distribution were first observed after 20 min of toxin exposure. The AAPs appeared to detach from focal contacts on the cytoplasmic surface of the plasma membrane, condense into cytoplasmic aggregates, and ultimately collapse into a juxtanuclear bundle. The results of this study indicate that, in hepatocytes exposed to MCLR, the collapse of actin MFs occurs prior to the dislocation of α‐actinin and talin. Changes in these actin associated proteins are not likely to account for the initial changes in actin MFs. © 1995 Wiley‐Liss, Inc.

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