Next Article in Journal
Candida Administration in Bilateral Nephrectomy Mice Elevates Serum (1→3)-β-D-glucan That Enhances Systemic Inflammation Through Energy Augmentation in Macrophages
Next Article in Special Issue
The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know
Previous Article in Journal
Role of Carbonic Anhydrase in Cerebral Ischemia and Carbonic Anhydrase Inhibitors as Putative Protective Agents
Previous Article in Special Issue
A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice
Communication

Differences in Recycling of Apolipoprotein E3 and E4—LDL Receptor Complexes—A Mechanistic Hypothesis

by 1,* and 1,2,*
1
Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA
2
Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnic University, 195251 St. Petersburg, Russia
*
Authors to whom correspondence should be addressed.
Academic Editor: Michael Ugrumov
Int. J. Mol. Sci. 2021, 22(9), 5030; https://doi.org/10.3390/ijms22095030
Received: 26 April 2021 / Revised: 5 May 2021 / Accepted: 7 May 2021 / Published: 10 May 2021
Apolipoprotein E (ApoE) is a protein that plays an important role in the transport of fatty acids and cholesterol and in cellular signaling. On the surface of the cells, ApoE lipoparticles bind to low density lipoprotein receptors (LDLR) that mediate the uptake of the lipids and downstream signaling events. There are three alleles of the human ApoE gene. Presence of ApoE4 allele is a major risk factor for developing Alzheimer’s disease (AD) and other disorders late in life, but the mechanisms responsible for biological differences between different ApoE isoforms are not well understood. We here propose that the differences between ApoE isoforms can be explained by differences in the pH-dependence of the association between ApoE3 and ApoE4 isoforms and LDL-A repeats of LDLR. As a result, the following endocytosis ApoE3-associated LDLRs are recycled back to the plasma membrane but ApoE4-containing LDLR complexes are trapped in late endosomes and targeted for degradation. The proposed mechanism is predicted to lead to a reduction in steady-state surface levels of LDLRs and impaired cellular signaling in ApoE4-expressing cells. We hope that this proposal will stimulate experimental research in this direction that allows the testing of our hypothesis. View Full-Text
Keywords: ApoE; LDL receptor; endosome; Alzheimer’s disease; modelling; protonation; charged interaction ApoE; LDL receptor; endosome; Alzheimer’s disease; modelling; protonation; charged interaction
Show Figures

Figure 1

MDPI and ACS Style

Kim, M.; Bezprozvanny, I. Differences in Recycling of Apolipoprotein E3 and E4—LDL Receptor Complexes—A Mechanistic Hypothesis. Int. J. Mol. Sci. 2021, 22, 5030. https://doi.org/10.3390/ijms22095030

AMA Style

Kim M, Bezprozvanny I. Differences in Recycling of Apolipoprotein E3 and E4—LDL Receptor Complexes—A Mechanistic Hypothesis. International Journal of Molecular Sciences. 2021; 22(9):5030. https://doi.org/10.3390/ijms22095030

Chicago/Turabian Style

Kim, Meewhi, and Ilya Bezprozvanny. 2021. "Differences in Recycling of Apolipoprotein E3 and E4—LDL Receptor Complexes—A Mechanistic Hypothesis" International Journal of Molecular Sciences 22, no. 9: 5030. https://doi.org/10.3390/ijms22095030

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop