Research Topics
| James ShorterSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
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Detail Information
Publications
Prions as adaptive conduits of memory and inheritanceJames Shorter
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Nat Rev Genet 6:435-50. 2005..We then describe situations in which prion-enciphered events might have essential roles in long-term memory formation, transcriptional memory and genome-wide expression patterns...
Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activitiesJames Shorter
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Mol Cell 23:425-38. 2006..In vivid distinction, the endpoint of Ure2 fragmentation is short prion fibers with enhanced infectivity and self-replicating ability. These advances explain the distinct effects of Hsp104 on the inheritance of the two prions...- Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformersJames Shorter
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Science 304:1793-7. 2004..These Hsp104 activities differed in their reaction mechanism and can explain [PSI+] inheritance patterns... - Prime time for alpha-synucleinAaron D Gitler
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
J Neurosci 27:2433-4. 2007 - The Parkinson's disease protein alpha-synuclein disrupts cellular Rab homeostasisAaron D Gitler
Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 105:145-50. 2008..Thus, alpha-syn causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive... - Direct and selective elimination of specific prions and amyloids by 4,5-dianilinophthalimide and analogsHuan Wang
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 805b Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 105:7159-64. 2008..Our studies provide mechanistic insights and reinvigorate hopes for small-molecule therapies that specifically disrupt intermolecular amyloid contacts... - Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prionsJames Shorter
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Stellar Chance Laboratories, Philadelphia, PA 19104, USA
EMBO J 27:2712-24. 2008..This activity is reduced when Ssa1, or enhanced when Ssb1, is incorporated into nascent prions. These findings illuminate several facets of the chaperone interplay that underpins [PSI(+)] inheritance... - Asymmetric deceleration of ClpB or Hsp104 ATPase activity unleashes protein-remodeling activityShannon M Doyle
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health NIH, Bethesda, Maryland 20892, USA
Nat Struct Mol Biol 14:114-22. 2007..We suggest that this versatility in reaction mechanism enables ClpB and Hsp104 to reactivate the entire aggregated proteome after stress and enables Hsp104 to control prion inheritance... - Atypical AAA+ subunit packing creates an expanded cavity for disaggregation by the protein-remodeling factor Hsp104Petra Wendler
Department of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK
Cell 131:1366-77. 2007..The large cavity could enable the uptake of polypeptide loops without a requirement for exposed N or C termini... - Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by two discrete activitiesHeather Sadlish
Zentrum für Molekulare Biologie der Universität Heidelberg ZMBH, DKFZ ZMBH Alliance, Universitat Heidelberg, Heidelberg, Germany
PLoS ONE 3:e1763. 2008..This activity is not essential for prion formation under conditions of Sup35 overproduction, however, it may be relevant for spontaneous [PSI(+)] formation as well as for protection of the prion trait upon physiological Hsp104 induction... - A cryptic Rab1-binding site in the p115 tethering proteinMatthew Beard
Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA
J Biol Chem 280:25840-8. 2005..Regulation of this interaction by proteins such as GM130 and Giantin may control the membrane recruitment of p115 by Rab1... - Hsp104 antagonizes alpha-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson diseaseChristophe Lo Bianco
Wallenberg Neuroscience Center, Division of Neurobiology, Department of Experimental Medical Science, Lund University, Lund, Sweden
J Clin Invest 118:3087-97. 2008..Hsp104 likely protects dopaminergic neurons by antagonizing toxic alpha-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses... - Hsp104: a weapon to combat diverse neurodegenerative disordersJames Shorter
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
Neurosignals 16:63-74. 2008..Here, I review the modus operandi of Hsp104 and showcase efforts to unleash Hsp104 on the protein-misfolding events connected to disparate neurodegenerative amyloidoses...