Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity
Abstract
Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.
- Authors:
-
- Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India)
- Publication Date:
- OSTI Identifier:
- 22416866
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 456; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; AGGLOMERATION; DISEASES; GLUTAMINE; LOSSES; MUTANTS; NERVE CELLS; ORGANIC POLYMERS; PROTEINS; TOXICITY
Citation Formats
Choudhury, Kamalika Roy, Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, and Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity. United States: N. p., 2015.
Web. doi:10.1016/J.BBRC.2014.11.035.
Choudhury, Kamalika Roy, Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, & Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity. United States. https://doi.org/10.1016/J.BBRC.2014.11.035
Choudhury, Kamalika Roy, Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, and Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com. 2015.
"Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity". United States. https://doi.org/10.1016/J.BBRC.2014.11.035.
@article{osti_22416866,
title = {Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity},
author = {Choudhury, Kamalika Roy and Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 and Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com},
abstractNote = {Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.},
doi = {10.1016/J.BBRC.2014.11.035},
url = {https://www.osti.gov/biblio/22416866},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 456,
place = {United States},
year = {Fri Jan 02 00:00:00 EST 2015},
month = {Fri Jan 02 00:00:00 EST 2015}
}