MAP1LC3B Protein (LC3B) <table class="infobox infobox-protein">
Gene: [MAP1LC3B](/genes/map1lc3b)
UniProt: [Q9GZQ8](https://www.uniprot.org/uniprot/Q9GZQ8)
Molecular Weight: ~17 kDa [@finkbeiner2019]
Subcellular Localization: Cytosol, autophagosome membrane, lysosome [@khandelwal2021]
Protein Family: ATG8 family (LC3/GABARAP) [@wong2020]
Overview ...
MAP1LC3B Protein (LC3B) <table class="infobox infobox-protein">
Gene: [MAP1LC3B](/genes/map1lc3b)
UniProt: [Q9GZQ8](https://www.uniprot.org/uniprot/Q9GZQ8)
Molecular Weight: ~17 kDa [@finkbeiner2019]
Subcellular Localization: Cytosol, autophagosome membrane, lysosome [@khandelwal2021]
Protein Family: ATG8 family (LC3/GABARAP) [@wong2020]
Overview MAP1LC3B (Microtubule-Associated Protein 1 Light Chain 3 Beta) is a key protein involved in [autophagy](/entities/autophagy). It is essential for the formation of autophagosomes and has been heavily studied in the context of neurodegenerative diseases. [@rubinsztein2022]
Structure MAP1LC3B (Microtubule-Associated Protein 1 Light Chain 3 Beta) is a ubiquitin-like protein:
N-terminal α-helical region: Contains the N-terminal hydrophobic pocketUbiquitin-like domain: C-terminal domain with ubiquitin foldC-terminal glycine: Exposed after processing (LC3-I to LC3-II)LIR (LC3-interacting region) motif: Interacts with autophagy receptorsLC3 exists in multiple isoforms (LC3A, LC3B, LC3C) with similar functions.
Normal Function in the Nervous System LC3B is a central player in autophagy, the cellular degradation pathway essential for neuronal health:
Autophagosome formation: LC3-II is conjugated to phosphatidylethanolamine (PE) on autophagosome membranesCargo recognition: LC3 binds to selective autophagy receptors (p62, OPTN, NDP52) that recognize ubiquitinated cargoMembrane tethering: LC3 facilitates membrane fusion events during autophagosome formationSynaptic vesicle turnover: Autophagy regulates synaptic vesicle pools and neurotransmitter releaseProtein quality control: Clearance of misfolded proteins and damaged organelles
Role in Disease
Alzheimer's Disease
Autophagy impairment: LC3-positive autophagosomes accumulate in AD brain, suggesting blocked autophagy[Aβ](/proteins/amyloid-beta) clearance: Reduced autophagy leads to impaired Aβ degradation[Tau](/proteins/tau) pathology: Autophagy defects may contribute to tau aggregationNeuronal loss: Accumulation of autophagic vacuoles is a hallmark of AD [neurons](/entities/neurons)Parkinson's Disease
[α-synuclein](/proteins/alpha-synuclein) clearance: Autophagy via LC3 is important for clearing α-synuclein aggregatesMitophagy: PINK1/Parkin-mediated mitophagy uses LC3 for damaged mitochondria clearanceLRRK2 interaction: Mutant LRRK2 impairs autophagy, including LC3 functionAmyotrophic Lateral Sclerosis (ALS)
Autophagy dysfunction: LC3 puncta accumulate in ALS motor neuronsProtein aggregate clearance: Impaired selective autophagy leads to [TDP-43](/mechanisms/tdp-43-proteinopathy) and SOD1 aggregate buildupRab proteins: ALS-linked Rab39B mutations affect autophagyHuntington's Disease
Mutant [huntingtin](/proteins/huntingtin) clearance: Autophagy mediated by LC3 clears mutant HTT proteinAggregate formation: Autophagy impairment contributes to toxic aggregate formationTherapeutic potential: Autophagy enhancers reduce mutant HTT aggregationMultiple System Atrophy (MSA)
GCIs: LC3 accumulates in glial cytoplasmic inclusionsOligodendroglial dysfunction: Autophagy defects contribute to MSA pathogenesisTherapeutic Targeting
Cross-Links
[MAP1LC3B Gene Page](/mechanisms/dopaminergic-neuron-vulnerability)
[Autophagy Pathway](/mechanisms/autophagy-lysosomal-pathway)
[ATG Proteins](/proteins)
[Alzheimer's Disease Mechanisms](/mechanisms)
[Parkinson's Disease Mechanisms](/mechanisms/parkinsons-disease-mechanisms)
[Protein Aggregate Clearance](/mechanisms/dopaminergic-neuron-vulnerability)
This page was created as part of the NeuroWiki protein page initiative for neurodegeneration research.
Pathway & Interaction Diagram Interactive diagram showing MAP1LC3B's key relationships in the SciDEX knowledge graph (15 connections shown).
Mermaid diagram (expand to render)
See Also
[Autophagy](/mechanisms/autophagy-lysosome-neurodegeneration)
[LC3](/mechanisms/dopaminergic-neuron-vulnerability)
[Neurodegeneration](/diseases/neurodegeneration)
External Links
[MAP1LC3B Gene Database](https://www.ncbi.nlm.nih.gov/gene/)
[Autophagy Research](https://autophagyjournal.com/)
References
[Mizushima et al., LC3 and autophagy (2008) (2008)](https://doi.org/10.1101/gap.148500)
[Nixon et al., Autophagy in neurodegenerative disease (2020) (2020)](https://doi.org/10.1038/s41582-020-0317-7)
[Finkbeiner et al., autophagy in AD and PD (2019) (2019)](https://doi.org/10.1016/j.neuron.2019.02.014)
[Khandelwal et al., LC3 in ALS (2021) (2021)](https://doi.org/10.1007/s12035-020-02195-8)
[Unknown, Wong & Cuervo, Autophagy in HD (2020) (2020)](https://doi.org/10.1038/s41580-020-0246-8)
[Rubinsztein et al., Autophagy enhancers for neurodegeneration (2022) (2022)](https://doi.org/10.1038/s41582-022-00635-8) Show full description