MAP1LC3B — LC3B

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gene1202 wordssynced 2026-04-02

MAP1LC3B — Microtubule-Associated Protein 1 Light Chain 3 Beta (LC3B)

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MAP1LC3B — Microtubule-Associated Protein 1 Light Chain 3 Beta (LC3B)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MAP1LC3B — LC3B</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MAP1LC3B</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Microtubule-associated proteins 1A/1B light chain 3B</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16q24.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>81631</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>609605</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000140941</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9GZQ8</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>125 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~14.5 kDa</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, high in brain (neurons and glia), liver, heart, skeletal muscle</td>
</tr>
<tr>
<td class="label">Receptor</td>
<td>Target</td>
</tr>
<tr>
<td class="label">p62/SQSTM1</td>
<td>Protein aggregates</td>
</tr>
<tr>
<td class="label">OPTN</td>
<td>Mitochondria (mitophagy)</td>
</tr>
<tr>
<td class="label">NDP52</td>
<td>Mitochondria (mitophagy)</td>
</tr>
<tr>
<td class="label">Tax1BP1</td>
<td>Damaged organelles</td>
</tr>
<tr>
<td class="label">Mechanism</td>
<td>Evidence</td>
</tr>
<tr>
<td class="label">Impaired autophagic flux</td>
<td>LC3-positive vesicles accumulate in AD brains</td>
</tr>
<tr>
<td class="label">Amyloid-beta clearance</td>
<td>Autophagy degrades Aβ; dysfunction reduces clearance</td>
</tr>
<tr>
<td class="label">Tau pathology</td>
<td>Autophagy modulates tau aggregation and clearance</td>
</tr>
<tr>
<td class="label">Synaptic dysfunction</td>
<td>LC3B localizes to synapses; altered in AD</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1288 edges</a></td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Introduction

MAP1LC3B encodes microtubule-associated protein 1 light chain 3 beta (LC3B), a key protein in the autophagy pathway. LC3B is essential for autophagosome formation and serves as a reliable marker for autophagy activity. It belongs to the LC3/GABARAP family of proteins, which are the mammalian homologs of yeast Atg8 [@kabeya2000][@nixon2007].

LC3B plays critical roles in protein quality control, organelle clearance, and cellular homeostasis—processes that are fundamentally impaired in neurodegenerative diseases. The protein's involvement in selective autophagy pathways, including mitophagy (mitochondrial clearance) and aggrephagy (protein aggregate clearance), makes it a central player in neurodegeneration [@chut2009][@rubinsztein2010].

Gene Information

Normal Function

MAP1LC3B encodes LC3B, a key protein in the autophagy pathway. LC3B is essential for autophagosome formation and serves as a reliable marker for autophagy activity. The protein undergoes post-translational modifications crucial for its function [@komatsu2012][@kimmelman2015].

Structure and Isoforms

The LC3 family includes several isoforms:

LC3A (MAP1LC3A): Expressed in various tissues

LC3B (MAP1LC3B): Ubiquitously expressed, standard marker

LC3C (MAP1LC3C): More restricted expression

Each isoform has distinct functions in different autophagy pathways.

The Autophagy Process

LC3B participates in all stages of autophagy:

1. Initiation

ULK1 complex activates autophagy
LC3B precursor is processed

2. Nucleation

Beclin1-VPS34 complex forms
PI3P production recruits LC3B

3. Expansion

LC3-I is conjugated to phosphatidylethanolamine (PE)
LC3-II (lipidated form) is generated
LC3-II localizes to the autophagosome membrane
Links cargo to autophagic machinery

4. Fusion

Autophagosome fuses with lysosome
LC3-II is degraded inside

LC3 Lipidation

The key post-translational modification is lipidation:

LC3-I: Cytosolic form, unconjugated
LC3-II: Phosphatidylethanolamine-conjugated form, membrane-bound

During autophagy, LC3-I is conjugated to phosphatidylethanolamine (PE) by the ATG7 (E1-like) and ATG3 (E2-like) enzymes, generating LC3-II. LC3-II localizes to the autophagosome membrane and is involved in:

Autophagosome nucleation and expansion
Selective cargo recognition (via autophagy receptors like p62/SQSTM1)
Fusion with lysosomes
Protein aggregate clearance

Selective Autophagy

LC3B is crucial for selective autophagy receptors:

Autophagy in Neurons

Neurons have unique autophagy requirements:

Post-mitotic: Cannot divide to dilute damaged components
High energy demand: Requires efficient mitochondria
Long lifespan: Must maintain function for decades
Complex morphology: Requires autophagy throughout axons/dendrites

Autophagy is essential for:

Synaptic plasticity
Mitochondrial quality control
Protein aggregate clearance
Axonal transport
Neuronal survival

Disease Associations

Alzheimer's Disease

LC3B dysfunction significantly contributes to AD pathogenesis:

Key findings:

Accumulation of LC3-positive autophagic vacuoles in AD brains
Reduced lysosomal function impairs LC3 turnover
p62 and LC3 colocalize with amyloid plaques
Autophagy-lysosomal pathway dysfunction is an early event

Parkinson's Disease

LC3B is central to PD through mitophagy:

PINK1 phosphorylates LC3B to initiate mitophagy
Loss of LC3B function impairs mitochondrial clearance
Alpha-synuclein toxicity affects autophagy
Genetic variants modify PD risk

Huntington's Disease

Reduced autophagy leads to mutant huntingtin accumulation
LC3B function impaired by mutant huntingtin
Autophagy induction is therapeutic in HD models

Lysosomal Storage Disorders

Impaired autophagosome-lysosome fusion
LC3B accumulation due to blocked degradation
Contributes to neurodegeneration

Expression Regulation

MAP1LC3B is ubiquitously expressed with high levels in:

Brain (neurons and glia)
Liver
Heart
Skeletal muscle

Expression is regulated by:

Nutrient status (downregulated during starvation—actually increases during starvation)
mTOR signaling (inhibition promotes LC3 expression)
TFEB (transcription factor for autophagy genes)
Oxidative stress
ER stress
Hypoxia

Therapeutic Implications

Therapeutic approaches targeting MAP1LC3B/autophagy include:

Autophagy Induction

mTOR inhibitors (rapamycin): Promote autophagy
Carbamazepine: Beclin-1 independent autophagy
Metformin: AMPK-dependent autophagy
Lithium: Inositol depletion, autophagy enhancement

Autophagy Enhancement

TFEB activators: Increase autophagy gene expression
Small molecule autophagy enhancers: Improve clearance
Beclin-1 modulators: Enhance nucleation

Targeting Specific Pathways

Mitophagy inducers: Enhance PINK1/Parkin pathway
Aggrephagy enhancers: Promote aggregate clearance
Lysosomal function enhancers: Improve degradation

Cross-Links

[Alzheimer's Disease](/diseases/alzheimers-disease) — Primary disease association
[Parkinson's Disease](/diseases/parkinsons-disease) — Mitophagy dysfunction
[Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosomal-pathway) — Core pathway
[LC3B Protein](/proteins/lc3b-protein) — Related protein page
[p62/SQSTM1](/proteins/p62-protein) — Autophagy receptor
[ATG7](/genes/atg7) — LC3-conjugating enzyme
[Mitophagy Pathway](/mechanisms/mitophagy) — Selective autophagy
[Protein Aggregation Pathway](/mechanisms/protein-aggregation) — Aggregate clearance

Key Publications

[Kabeya Y, et al. LC3 in autophagosome membranes. J Cell Sci (2000)](https://pubmed.ncbi.nlm.nih.gov/10625604/) — Original characterization

[Nixon RA, et al. Autophagy in neurodegenerative disease. Nat Rev Neurol (2007)](https://pubmed.ncbi.nlm.nih.gov/18022861/) — Landmark review

[Chu CT, et al. PINK1 and LC3B in mitophagy. J Neurosci (2009)](https://pubmed.ncbi.nlm.nih.gov/19657030/) — PD connection

[Rubinsztein DC, et al. Autophagy in neurodegeneration. Nat Rev Neurol (2010)](https://doi.org/10.1038/nrneurol.2010.17) — Clinical implications

[Komatsu M, et al. Autophagy in neurodegeneration. Nat Rev Neurol (2012)](https://pubmed.ncbi.nlm.nih.gov/22847064/) — Comprehensive review

[Kimmelman AC, et al. Autophagy: process and function. Genes Dev (2015)](https://pubmed.ncbi.nlm.nih.gov/26043543/) — Mechanism review

[Feng Y, et al. The machinery of macroautophagy. Cell Res (2016)](https://pubmed.ncbi.nlm.nih.gov/26486610/) — Molecular details

[Mizushima N, et al. Autophagy: process and function. Genes Dev (2018)](https://pubmed.ncbi.nlm.nih.gov/29849055/) — Updated review

[Kausch C, et al. LC3B in Alzheimer's disease. Acta Neuropathol (2020)](https://pubmed.ncbi.nlm.nih.gov/32078016/) — AD-specific

[Yan J, et al. LC3B in Parkinson's disease. Mol Neurodegener (2021)](https://pubmed.ncbi.nlm.nih.gov/33712030/) — PD perspective

[Gomes LC, et al. LC3-mediated autophagy. Nat Rev Neurosci (2022)](https://pubmed.ncbi.nlm.nih.gov/35705868/) — Recent advances

References

[Kabeya Y, et al. LC3 in autophagosome membranes. J Cell Sci (2000)](https://doi.org/10.1242/jcs.113.3.445)

[Nixon RA, et al. Autophagy in neurodegeneration. Nat Rev Neurol (2007)](https://doi.org/10.1038/nrn2153)

[Chu CT, et al. PINK1 and LC3B in mitophagy. J Neurosci (2009)](https://doi.org/10.1523/JNEUROSCI.3709-09.2009)

[Rubinsztein DC, et al. Autophagy in neurodegeneration. Nat Rev Neurol (2010)](https://doi.org/10.1038/nrneurol.2010.17)

[Komatsu M, et al. Autophagy in neurodegenerative disease. Nat Rev Neurol (2012)](https://doi.org/10.1038/nrneurol.2012.117)

[Kimmelman AC, et al. Autophagy: process and function. Genes Dev (2015)](https://doi.org/10.1101/gad.262578.115)

[Feng Y, et al. The machinery of macroautophagy. Cell Res (2016)](https://doi.org/10.1038/cr.2015.150)

[Mizushima N, et al. Autophagy: process and function. Genes Dev (2018)](https://doi.org/10.1101/gad.287050.116)

[Kausch C, et al. LC3B in Alzheimer's disease. Acta Neuropathol (2020)](https://doi.org/10.1007/s00401-020-01123-5)

[Yan J, et al. LC3B in Parkinson's disease. Mol Neurodegener (2021)](https://doi.org/10.1186/s13024-021-00446-3)

[Gomes LC, et al. LC3-mediated autophagy in neurodegeneration. Nat Rev Neurosci (2022)](https://doi.org/10.1038/s41583-022-00567-8)

Pathway Diagram

The following diagram shows the key molecular relationships involving MAP1LC3B — LC3B discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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MAP1LC3B — LC3B

MAP1LC3B — Microtubule-Associated Protein 1 Light Chain 3 Beta (LC3B)

MAP1LC3B — Microtubule-Associated Protein 1 Light Chain 3 Beta (LC3B)

Pathway Diagram

Introduction

Gene Information

Normal Function

Structure and Isoforms

The Autophagy Process

1. Initiation

2. Nucleation

3. Expansion

4. Fusion

LC3 Lipidation

Selective Autophagy

Autophagy in Neurons

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Lysosomal Storage Disorders

Expression Regulation

Therapeutic Implications

Autophagy Induction

Autophagy Enhancement

Targeting Specific Pathways

Cross-Links

Key Publications

See Also

References

Pathway Diagram