LC3GABARAP

LC3GABARAP refers to the mammalian ATG8 family of ubiquitin-like proteins that regulate autophagy, including the LC3 subfamily (MAP1LC3A, MAP1LC3B, MAP1LC3C) and the GABARAP subfamily (GABARAP, GABARAPL1, GABARAPL2). These proteins share a conserved ubiquitin-like fold and are synthesized as proproteins that undergo C-terminal processing to reveal a glycine essential for conjugation to lipid membranes.

In autophagy, LC3GABARAP proteins are processed by ATG4, activated by the E1-like enzyme ATG7 and the E2-like enzyme ATG3, and conjugated to phosphatidylethanolamine on the expanding phagophore membrane. This lipidation converts soluble cytosolic forms (LC3-I and GABARAP-I) into membrane-associated forms (LC3-II and GABARAP-II), which decorate autophagosomes and help recruit cargo receptors such as p62/SQSTM1 and NDP52. The family participates in both general autophagy and selective autophagy, aiding autophagosome formation, maturation, and fusion with lysosomes, often through interactions with other autophagy-related proteins and trafficking factors.

Subfamilies within the group show overlapping but distinct roles. LC3 proteins are commonly used as general autophagy markers, with LC3B being a frequently measured isoform, whereas GABARAPs are increasingly recognized for functions in late-stage autophagosome maturation, trafficking, and tethering to lysosomes. Expression and activity of these proteins are modulated by cellular stress and developmental context.

Beyond autophagy, LC3GABARAP proteins influence intracellular trafficking and membrane dynamics in some cell types, reflecting their broader roles in maintaining cellular homeostasis.