Stains
Light Chain 3B (LC3B)

Author: Satbir Thakur, Ph.D. (see Authors page)
Editor: Emeka Enwere, M.D.

Revised: 13 February 2017, last major update February 2017

Copyright: (c) 2017, PathologyOutlines.com, Inc.

PubMed Search: light chain 3B OR LC3B
Cite this page: Light Chain 3B (LC3B). PathologyOutlines.com website. http://pathologyoutlines.com/topic/stainslc3b.html. Accessed December 18th, 2017.
Definition / general
  • A ubiquitin-like modifier protein that is a member of the highly conserved autophagy related protein-8 (ATG8) protein family
  • Involved in cellular processes like autophagy, autophagosomal assembly, regulation of mitophagy and cellular response to nitrogen starvation
Essential features
  • Autophagy is a survival mechanism adopted by cells to maintain energy homeostasis and remove pathogens, toxic protein aggregates and old or damaged organelles (Cell 2008;132:27)
  • In metabolic stress conditions or with insufficient nutrient supply, the process of autophagy is rapidly upregulated to meet energy requirements and to provide building blocks for essential cellular functions (FASEB J 2016;30:3961)
  • Dysregulation of autophagy can cause accumulation of damaged protein and organelle aggregates, which may lead to cell death and organ failure (Nature 2006;441:880, J Cell Biol 2005;169:425)
  • LC3B is the most studied protein involved in autophagy and is essential for its execution; therefore, LC3B levels are widely used as marker for autophagy activity in a cell
Terminology
  • Also known as:
    • Autophagy related protein LC3 B
    • Autophagy related ubiquitin-like modifier LC3 B
    • MAP1 light chain 3-like protein 2
    • MAP1A / 1BLC3
    • MAP1A / MAP1B LC3 B
    • MAP1A / MAP1B light chain 3 B
    • MAP1ALC3
    • MAP1LC3B
    • Microtubule associated protein 1 light chain 3 beta
    • Microtubule associated proteins 1A / 1B light chain 3
    • Microtubule associated proteins 1A / 1B light chain 3B
    • MLP3B
    • Reference: PhosphoSitePlus
Sites
  • Cytoplasm, cytoplasmic vesicle, cytoskeleton, mitochondria, microtubule (UniProt)
Pathophysiology
  • The LC3 / GABA type-A receptor activated protein (GABARAP) family proteins are produced from separate transcripts, derived from their own genomic location
  • Each LC3 / GABARAP family protein is characterized by 2 N-terminal α-helices and a C-terminal ubiquitin core (FASEB J 2016;30:3961, Genes Cells 2004;9:611)
  • All LC3 proteins (LC3A, LC3C, GABARAP-1, -2) share sequence similarity with LC3B and have a conserved C-terminal glycine residue
  • LC3 proteins are primarily involved in the elongation of the phagophore membrane, whereas the GABARAP subfamily is essential for a later stage in autophagosome maturation
  • LC3B also plays a role in mitophagy, which regulates the number of mitochondria in a cell by eliminating them to a basal level to fulfill cellular energy requirements and preventing excess reactive oxygen species (ROS) production (GeneCards)
  • Cells deficient in the LC3 subfamily (LC3A-C) have impaired autophagosome formation; knockdown of LC3 subfamily leads to smaller autophagosomes and re-expression of LC3B can rescue phagophore elongation (EMBO J 2010;29:1792)
  • For clearance of intracellular salmonella, interaction between LC3B and -C, GABARAPL1 and -2, and Tax1 binding protein (TAX1BP)-1 is essential (PLoS Pathog 2016;12:e1005433)
Clinical features
    High expression as a favorable prognostic marker:
  • Colorectal cancer: high LC3B expression correlates with improved survival after surgery (Int J Clin Exp Pathol 2015;8:3882)
  • Esophageal adenocarcinoma: low LC3B and p62 expression is associated with poorer prognosis and more aggressive tumors (Oncotarget 2016;7:39241)

High expression as a negative prognostic marker:
  • Clear cell renal cell carcinoma: patients with high grade tumors showed increased levels of LC3B and concomitant decreased levels of miR-204, indicating that LC3B mediated macroautophagy is necessary for progression (Cancer Cell 2012;21:532)
  • Lacrimal gland adenoid cystic carcinoma: poorer disease free survival was found to be associated with higher expression of LC3B (Yonsei Med J 2016;57:482)
  • Retinoblastoma: high levels of LC3B and p62 are significantly associated with disease progression and tumor invasion (Eur Rev Med Pharmacol Sci 2016;20:3152)

Mouse models:
  • Pharmacological activation of autophagy (detected by LC3B levels) allows the survival of mouse pheochromocytoma cells in stressful conditions (Int J Cell Biol 2014;2014:135908)
  • LC3B (-/-) mice show decreased levels of apoptosis in the lungs after exposure to cigarette smoke and display resistance to cigarette smoke induced airspace enlargement; LC3B acts as a positive regulator of cigarette smoke induced lung epithelial cell death in experimental emphysema model (Proc Natl Acad Sci U S A 2010;107:18880)
  • LC3B null mice display higher pulmonary hypertension after exposure to chronic hypoxia as compared to wild type mice (Am J Respir Crit Care Med 2011;183:649)
  • Genetic deletion of autophagy proteins like Beclin 1 and LC3B in primary macrophages shows enhancement of mitochondrial ROS generation (Nat Immunol 2011;12:222)
Microscopic (histologic) images

Images hosted on other servers:

LC3B immunohistochemical staining

Virtual slides

Images hosted on other servers:

Testis tissue

Positive stains
  • LC3B is highly expressed in brain; pancreas, kidney, testis and placenta show moderate to low levels of LC3B (The Human Protein Atlas)
Negative stains
Additional references