title: Low molecular weight Abeta induces collapse of endoplasmic reticulum.
abstract: The endoplasmic reticulum (ER) is a dynamic multifunction organelle that is responsible for Ca(2+) homeostasis, protein folding, post-translational modification, protein degradation, and transportation of nascent proteins. Disruption of ER architecture might affect the normal physiology of the cell. In yeast, expansion of the ER is observed under unfolded protein response (UPR) and subsequently induces autophagy initiated from the ER. Here, we found that soluble low molecular weight of Abeta disrupted the anchoring between ER and microtubules (MT) and induced collapse of ER. In addition, it decreased the stability of MT. Subsequently, low molecular weight Abeta triggered autophagy and enhanced lysosomal degradation, as shown by electron microscopy and live-cell imaging. Dysfunction of ER can be further proved in postmortem AD brain and transgenic mice bearing APP Swedish mutation by immunohistochemical analysis of calreticulin. Treatment with Taxol, a MT-stabilizing agent, could partially inhibit collapse of the ER and induction of autophagy. The results show that Abeta-induced disruption of MT can affect the architecture of the ER. Collapse/aggregation of the ER may play an important role in Abeta peptide-triggered neurodegenerative processes.
authors.affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, L1-49, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Cora Sau-Wan
authors.initials: CS
authors.lastname: Lai
authors.forename: Julie
authors.initials: J
authors.lastname: Preisler
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.forename: Daniel Hong-Seng
authors.initials: DH
authors.lastname: Lee
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015739:Nocodazole / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D050257:Tubulin Modulators; D015739:Nocodazole