TY - JOUR
T1 - A membrane proximal helix in the cytosolic domain of the human APP interacting protein LR11/SorLA deforms liposomes
AU - Gill, Richard L.
AU - Wang, Xingsheng
AU - Tian, Fang
N1 - Funding Information:
We are grateful for the financial support from the National Institutes of Health ( R01GM105963-01A1 ) and the Penn State University College of Medicine . We thank Dr. J. M. Flanagan at the Penn State University College of Medicine for the helpful discussions, Drs. A. Benesi and E. Hatzakis at the NMR facility of the Penn State University, University Park for the assistance on the use of 850 MHz instrument, Dr. T. Fox at the Penn State University College of Medicine for the help in liposome preparation, and Mr. R. Myers at the Penn State College of Medicine Core Electron Microscopy Imaging Facility for the technical assistance of EM experiment. We would also like to thank the Penn State Automated Biological Calorimetry Facility — University Park, PA for the use of DLS instrument.
Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2015/1
Y1 - 2015/1
N2 - Over the last decade, compelling evidence has linked the development of Alzheimer's disease (AD) to defective intracellular trafficking of the amyloid precursor protein (APP). Faulty APP trafficking results in an overproduction of Aβ peptides, which is generally agreed to be the primary cause of AD-related pathogenesis. LR11 (SorLA), a type I transmembrane sorting receptor, has emerged as a key regulator of APP trafficking and processing. It directly interacts with APP and diverts it away from amyloidogenic processing. The 54-residue cytosolic domain of LR11 is essential for its proper intracellular localization and trafficking which, in turn, determines the fate of APP. Here, we have found a surprising membrane-proximal amphipathic helix in the cytosolic domain of LR11. Moreover, a peptide corresponding to this region folds into an α-helical structure in the presence of liposomes and transforms liposomes to small vesicles and tubule-like particles. We postulate that this amphipathic helix may contribute to the dynamic remodeling of membrane structure and facilitate LR11 intracellular transport. This article is part of a Special Issue entitled: NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces. Guest Editors: Lynette Cegelski and David P.Weliky.
AB - Over the last decade, compelling evidence has linked the development of Alzheimer's disease (AD) to defective intracellular trafficking of the amyloid precursor protein (APP). Faulty APP trafficking results in an overproduction of Aβ peptides, which is generally agreed to be the primary cause of AD-related pathogenesis. LR11 (SorLA), a type I transmembrane sorting receptor, has emerged as a key regulator of APP trafficking and processing. It directly interacts with APP and diverts it away from amyloidogenic processing. The 54-residue cytosolic domain of LR11 is essential for its proper intracellular localization and trafficking which, in turn, determines the fate of APP. Here, we have found a surprising membrane-proximal amphipathic helix in the cytosolic domain of LR11. Moreover, a peptide corresponding to this region folds into an α-helical structure in the presence of liposomes and transforms liposomes to small vesicles and tubule-like particles. We postulate that this amphipathic helix may contribute to the dynamic remodeling of membrane structure and facilitate LR11 intracellular transport. This article is part of a Special Issue entitled: NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces. Guest Editors: Lynette Cegelski and David P.Weliky.
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U2 - 10.1016/j.bbamem.2014.05.020
DO - 10.1016/j.bbamem.2014.05.020
M3 - Article
C2 - 24866012
AN - SCOPUS:84979850951
SN - 0005-2736
VL - 1848
SP - 323
EP - 328
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 1
ER -