PMID- 10491388
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 146
IP  - 6
DP  - 1999 Sep 20
TI  - Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera.
PG  - 1239-54
AB  - Formation of a novel structure, the aggresome, has been proposed to represent a
      general cellular response to the presence of misfolded proteins (Johnston, J.A., 
      C.L. Ward, and R.R. Kopito. 1998. J. Cell Biol. 143:1883-1898; Wigley, W.C., R.P.
      Fabunmi, M.G. Lee, C.R. Marino, S. Muallem, G.N. DeMartino, and P.J. Thomas.
      1999. J. Cell Biol. 145:481-490). To test the generality of this finding and
      characterize aspects of aggresome composition and its formation, we investigated 
      the effects of overexpressing a cytosolic protein chimera (GFP-250) in cells.
      Overexpression of GFP-250 caused formation of aggresomes and was paralleled by
      the redistribution of the intermediate filament protein vimentin as well as by
      the recruitment of the proteasome, and the Hsp70 and the chaperonin systems of
      chaperones. Interestingly, GFP-250 within the aggresome appeared not to be
      ubiquitinated. In vivo time-lapse analysis of aggresome dynamics showed that
      small aggregates form within the periphery of the cell and travel on microtubules
      to the MTOC region where they remain as distinct but closely apposed particulate 
      structures. Overexpression of p50/dynamitin, which causes the dissociation of the
      dynactin complex, significantly inhibited the formation of aggresomes, suggesting
      that the minus-end-directed motor activities of cytoplasmic dynein are required
      for aggresome formation. Perinuclear aggresomes interfered with correct Golgi
      localization and disrupted the normal astral distribution of microtubules.
      However, ER-to-Golgi protein transport occurred normally in aggresome containing 
      cells. Our results suggest that aggresomes can be formed by soluble,
      nonubiquitinated proteins as well as by integral transmembrane ubiquitinated
      ones, supporting the hypothesis that aggresome formation might be a general
      cellular response to the presence of misfolded proteins.
FAU - Garcia-Mata, R
AU  - Garcia-Mata R
AD  - Department of Cell Biology, University of Alabama at Birmingham, Birmingham,
      Alabama 35294, USA.
FAU - Bebok, Z
AU  - Bebok Z
FAU - Sorscher, E J
AU  - Sorscher EJ
FAU - Sztul, E S
AU  - Sztul ES
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Carrier Proteins)
RN  - 0 (Dynactin Complex)
RN  - 0 (G protein, vesicular stomatitis virus)
RN  - 0 (Golgi Matrix Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ubiquitins)
RN  - 0 (Vesicular Transport Proteins)
RN  - 0 (Vimentin)
RN  - 0 (Viral Envelope Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 162079-20-1 (vesicular transport factor p115)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.6.4.2 (Dyneins)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - COS Cells
MH  - Carrier Proteins/chemistry/genetics/*metabolism
MH  - Centrosome/metabolism/ultrastructure
MH  - Cysteine Endopeptidases/metabolism
MH  - Cytosol/chemistry/*metabolism/ultrastructure
MH  - Dynactin Complex
MH  - Dyneins/antagonists & inhibitors/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Golgi Apparatus/metabolism
MH  - Golgi Matrix Proteins
MH  - Green Fluorescent Proteins
MH  - Kinetics
MH  - Luminescent Proteins/genetics/*metabolism
MH  - *Membrane Glycoproteins
MH  - Membrane Proteins/chemistry/genetics/*metabolism
MH  - Microtubule-Associated Proteins/antagonists & inhibitors/metabolism
MH  - Microtubules/metabolism
MH  - Molecular Chaperones/metabolism
MH  - Multienzyme Complexes/metabolism
MH  - Organelles/*chemistry/*metabolism/ultrastructure
MH  - Peptide Fragments/chemistry/genetics/metabolism
MH  - Proteasome Endopeptidase Complex
MH  - Protein Folding
MH  - Protein Processing, Post-Translational
MH  - Recombinant Fusion Proteins/chemistry/genetics/*metabolism
MH  - Solubility
MH  - Ubiquitins/metabolism
MH  - *Vesicular Transport Proteins
MH  - Vimentin/metabolism
MH  - Viral Envelope Proteins/genetics/metabolism
PMC - PMC2156127
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
AID - 10.1083/jcb.146.6.1239 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Sep 20;146(6):1239-54. doi: 10.1083/jcb.146.6.1239.