Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Roy, Kasturi | Raychaudhuri, Mithu | Chakrabarti, Oishee | Mukhopadhyay, Debashis; *
Affiliations: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, WB, Kolkata, India
Correspondence: [*] Correspondence to: Debashis Mukhopadhyay, Ph.D., Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhan Nagar, West Bengal, Kolkata 700 064, India. Tel.: +91 33 2337 5345 49; Fax: +91 33 2337 4637; E-mail: [email protected].
Abstract: The ascertainment of elevated levels of amyloid-β protein precursor intracellular domain (AICD) in Alzheimer's disease (AD) brains and the fact that it contributes to AD-like pathology has geared the search toward a new paradigm. While studying endogenous as well as overexpressed Grb2-AICD interaction in AD cell models, it was found that Grb2 co-localized to compartments along with AICD. We report now that these vesicles form in a clathrin and dynamin independent manner. Both types of vesicles mature into autophagosomes, merge with lysosomes, and relieve the cells of AICD overload. Inhibiting autophagosome formation results in vesicle accumulation. AICD-level is reduced in Grb2 excess condition in Cycloheximide Chase setup. Reduced caspase activity and apoptosis point toward the fact that the cytotoxic effect of AICD is alleviated by its sequestration in autolysosomes. Hence we state that the entrapping of AICD in Grb2 vesicles and its clearance via autophagosomes is a survival contrivance on the part of the cell. This study unravels, for the first time, the roles of Grb2 in autophagy and in handling toxic protein overload in an AD-like scenario.
Keywords: Amyloid-β protein precursor protein, autophagy, CD63, clathrin, dynamin, Grb2, LC3 protein
DOI: 10.3233/JAD-130929
Journal: Journal of Alzheimer's Disease, vol. 38, no. 4, pp. 881-895, 2014
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
[email protected]
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office [email protected]
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
如果您在出版方面需要帮助或有任何建, 件至: [email protected]