The LC3 interactome at a glance

Abstract

Continuous synthesis of all cellular components requires their constant turnover in order for a cell to achieve homeostasis. To this end, eukaryotic cells are endowed with two degradation pathways -the ubiquitinproteasome system and the lysosomal pathway. The latter pathway is partly fed by autophagy, which targets intracellular material in distinct vesicles, termed autophagosomes, to the lysosome. Central to this pathway is a set of key autophagy proteins, including the ubiquitin-like modifier Atg8, that orchestrate autophagosome initiation and biogenesis. In higher eukaryotes, the Atg8 family comprises six members known as the light chain 3 (LC3) or c-aminobutyric acid (GABA)-receptorassociated protein (GABARAP) proteins. Considerable effort during the last 15 years to decipher the molecular mechanisms that govern autophagy has significantly advanced our understanding of the functioning of this protein family. In this Cell Science at a Glance article and the accompanying poster, we present the current LC3 protein interaction network, which has been and continues to be vital for gaining insight into the regulation of autophagy.

Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins

“…4A, B and D). Given the large number of LIR-containing proteins in mammalian genomes, 24,25 it is likely that other LIR motifs may also interact with Atg8-family proteins using a similar binding mode that we have discovered for FYCO1 LIR. Indeed, further sequence analysis of the currently known 43 In this presentation, the LC3A molecule is shown in the surface model and FYCO1 LIR in the ribbon-stick model.…”

“…Accumulating evidence showed that the specific interactions between Atg8-binding proteins and Atg8-family proteins were mainly mediated by a short motif named LC3-interacting region (LIR). [20][21][22][23][24][25][26][27][28][29] The canonical LIR motif has the consensus core sequence QxxG where Q being aromatic residues (W/F/Y), and G being bulk hydrophobic residues (L/I/ V). 17,26 Additional acidic residues and/or serine/threonine phosphorylation sites preceding the hydrophobic LIR core sequence are also commonly found in LIR-containing proteins, and are demonstrated to regulate their specific interactions with Atg8-family members.…”

The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy

“…One important function of LC3 is recruiting autophagic proteins to autophagosomes for assembly of functional autophagosomal complexes by interacting with the LIR (LC3-interacting region) domain-containing proteins. 18,19 Currently, more than 100 proteins have been identified containing the LIR domain. 19 One relevant example is the core autophagic protein SQSTM1/p62.…”

Differences of basic and induced autophagic activity between K562 and K562/ADM cells

“…LC3-Ⅱ is employed to the membrane of the autophagosome and specifically mediates elongation of the autophagosome. Therefore, the ratio of LC3-Ⅱ to LC3-Ⅰ will become larger when the quantity of autophagosomes increases (7). In addition to the shift of LC3-Ⅰ to LC3-Ⅱ, another crucial ATG protein P62 that interacts with ubiquitinated proteins through its UBA domain (ubiquitin-associated domain) and then delivers them to LC3-Ⅱ via another domain LIR (LC3-interacting region) will be finally degraded in the autolysosome, so the level of P62 has a contrary relationship with autophagic activity (8).…”