ArticleMolecular biology of the cell2018
GGA1 regulates signal-dependent sorting of BACE1 to recycling endosomes, which moderates Aβ production.
Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- GGAs: Regulation of Multiple Sorting Pathways and Potential Association With Human Diseases.Journal of cellular and molecular medicine · 2026Review
- Organelle perturbation in Alzheimer's disease: do intracellular amyloid-ß and the fragmented Golgi mediate early intracellular neurotoxicity?Frontiers in cell and developmental biology · 2025Review
- Article
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.The Biochemical journal · 2024Review
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Melatonergic Signaling Sustains Food Allergy Through FcεRI Recycling.Research (Washington, D.C.) · 2024Article
- Article
- Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice.Frontiers in aging neuroscience · 2024Article
- Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1.Stem cell reports · 2023Article
- APP-BACE1 Interaction and Intracellular Localization Regulate Aβ Production in iPSC-Derived Cortical Neurons.Cellular and molecular neurobiology · 2023Article
- A Polyaminobiaryl-Based β-secretase Modulator Alleviates Cognitive Impairments, Amyloid Load, Astrogliosis, and Neuroinflammation in APPInternational journal of molecular sciences · 2023Article
- Article
- Article
- The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes.Cellular and molecular life sciences : CMLS · 2022Article
- Integrating intracellular nanovesicles into integrin trafficking pathways and beyond.Cellular and molecular life sciences : CMLS · 2022Review
- Neuronal KCNQ2/3 channels are recruited to lipid raft microdomains by palmitoylation of BACE1.The Journal of general physiology · 2022Article
- Segregation of the membrane cargoes, BACE1 and amyloid precursor protein (APP) throughout the Golgi apparatus.Traffic (Copenhagen, Denmark) · 2022Article
- The understudied links of the retromer complex to age-related pathways.GeroScience · 2022Article
- Post-Translational Modifications of BACE1 in Alzheimer's Disease.Current neuropharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The diversion of the membrane-bound β-site amyloid precursor protein-(APP) cleaving enzyme (BACE1) from the endolysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the sorting nexin 4 (SNX4)-mediated, signal-independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the DXXLL-motif sequence DISLL in the cytoplasmic tail of BACE1. The phosphomimetic S498D BACE1 mutant was trafficked to recycling endosomes at a faster rate compared with wild-type BACE1 or the nonphosphorylatable S498A mutant. The rapid transit of BACE1 S498D from early endosomes was coupled with reduced levels of amyloid precursor protein processing and Aβ production, compared with the S498A mutant. We show that the adaptor, GGA1, and retromer are essential to mediate rapid trafficking of phosphorylated BACE1 to recycling endosomes. In addition, the BACE1 DISLL motif is phosphorylated and regulates endosomal trafficking, in primary neurons. Therefore, post-translational phosphorylation of DISLL enhances the exit of BACE1 from early endosomes, a pathway mediated by GGA1 and retromer, which is important in regulating Aβ production.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.