ArticleMolecular neurodegeneration2014
Axonal BACE1 dynamics and targeting in hippocampal neurons: a role for Rab11 GTPase.
Article in Molecular neurodegeneration, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 201 citations in OpenAlex.
- Abl kinase activation promotes axon initial segment disassembly and protein sorting defects in Alzheimer's disease.BMC biology · 2026Article
- CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex-specific alteration of multiple proteins involved in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Experimental methods for studying amyloid cross-interactions.Protein science : a publication of the Protein Society · 2025Review
- 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
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Kismet/CHD7/CHD8 and Amyloid Precursor Protein-like Regulate Synaptic Levels of Rab11 at theInternational journal of molecular sciences · 2024Article
- Rhei Undulati Rhizoma attenuates memory decline and reduces amyloid-β induced neuritic dystrophy in 5xFAD mouse.Chinese medicine · 2024Article
- Genetic architecture of hippocampus subfields volumes in Alzheimer's disease.CNS neuroscience & therapeutics · 2024Article
- Investigation of Potential Drug Targets Involved in Inflammation Contributing to Alzheimer's Disease Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment.Cell reports · 2023Article
- Rab11A Depletion in Microglia-Derived Extracellular Vesicle Proteome upon Beta-Amyloid Treatment.Cell biochemistry and biophysics · 2023Article
- 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
- Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3.The Journal of cell biology · 2022Article
- Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer's Disease.Biomedicines · 2022Review
- Neuronal KCNQ2/3 channels are recruited to lipid raft microdomains by palmitoylation of BACE1.The Journal of general physiology · 2022Article
- The Alzheimer susceptibility gene BIN1 induces isoform-dependent neurotoxicity through early endosome defects.Acta neuropathologica communications · 2022Article
- Secretases Related to Amyloid Precursor Protein Processing.Membranes · 2021Review
- Opposing functions for retromer and Rab11 in extracellular vesicle traffic at presynaptic terminals.The Journal of cell biology · 2021Article
- G-protein coupled receptor, PI3K and Rho signaling pathways regulate the cascades of Tau and amyloid-β in Alzheimer's disease.Molecular biomedicine · 2021Review
- Inactive variants of death receptor p75The EMBO journal · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundBACE1 is one of the two enzymes that cleave amyloid precursor protein to generate Alzheimer's disease (AD) beta amyloid peptides. It is widely believed that BACE1 initiates APP processing in endosomes, and in the brain this cleavage is known to occur during axonal transport of APP. In addition, BACE1 accumulates in dystrophic neurites surrounding brain senile plaques in individuals with AD, suggesting that abnormal accumulation of BACE1 at presynaptic terminals contributes to pathogenesis in AD. However, only limited information is available on BACE1 axonal transport and targeting.
resultsBy visualizing BACE1-YFP dynamics using live imaging, we demonstrate that BACE1 undergoes bi-directional transport in dynamic tubulo-vesicular carriers along axons in cultured hippocampal neurons and in acute hippocampal slices of transgenic mice. In addition, a subset of BACE1 is present in larger stationary structures, which are active presynaptic sites. In cultured neurons, BACE1-YFP is preferentially targeted to axons over time, consistent with predominant in vivo localization of BACE1 in presynaptic terminals. Confocal analysis and dual-color live imaging revealed a localization and dynamic transport of BACE1 along dendrites and axons in Rab11-positive recycling endosomes. Impairment of Rab11 function leads to a diminution of total and endocytosed BACE1 in axons, concomitant with an increase in the soma. Together, these results suggest that BACE1 is sorted to axons in endosomes in a Rab11-dependent manner.
conclusionOur results reveal novel information on dynamic BACE1 transport in neurons, and demonstrate that Rab11-GTPase function is critical for axonal sorting of BACE1. Thus, we suggest that BACE1 transcytosis in endosomes contributes to presynaptic BACE1 localization.
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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.