LC3-associated Phagocytosis (LAP) Pathway
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Questions and Answers

What is the function of autophagy receptors in selective autophagy?

  • To recruit phagophores to cargos through interaction with LC3II (correct)
  • To prevent the formation of autophagosomes
  • To degrade LC3II
  • To inhibit autophagy
  • What is the region on autophagy receptors that interacts with LC3II?

  • LIR (correct)
  • ULK1
  • UBD
  • NBR1
  • Which of the following is a type of selective autophagy receptor?

  • ULK1
  • p62 (correct)
  • ATG12
  • LC3
  • What is the function of the ULK1 complex in autophagy?

    <p>To initiate autophagy by phosphorylating ATG13</p> Signup and view all the answers

    What is the result of LC3 lipidation?

    <p>Formation of autophagosomes</p> Signup and view all the answers

    What is the function of ATG proteins in autophagy?

    <p>To facilitate autophagosome formation</p> Signup and view all the answers

    What is the region on autophagy receptors that interacts with ubiquitin?

    <p>UBD</p> Signup and view all the answers

    Which of the following is NOT a type of selective autophagy receptor?

    <p>ATG12</p> Signup and view all the answers

    What is a key characteristic of LC3-associated phagocytosis (LAP)?

    <p>It involves conjugation of LC3 family proteins to phagosome membranes.</p> Signup and view all the answers

    Which molecular complex is required for LC3-associated phagocytosis?

    <p>PI3KC3 complex.</p> Signup and view all the answers

    Which of the following statements about LAP is true?

    <p>LAP uses a portion of the canonical autophagy machinery.</p> Signup and view all the answers

    What types of materials can be targeted through LC3-associated phagocytosis?

    <p>Dying cells, immune complexes, and pathogens.</p> Signup and view all the answers

    What differentiates LAP from canonical autophagy?

    <p>LAP does not respond to intracellular stress sensing.</p> Signup and view all the answers

    Which of the following components is dispensable for LC3-associated phagocytosis?

    <p>ULK1.</p> Signup and view all the answers

    Which process is NOT associated with LC3-associated phagocytosis?

    <p>Degradation of nutrient-rich particles.</p> Signup and view all the answers

    What activates the LAP pathway?

    <p>External stimuli such as ligands and pathogens.</p> Signup and view all the answers

    What role do Atg8s play in autophagosome formation?

    <p>Regulate the expansion of autophagosomes</p> Signup and view all the answers

    Which ATG protein is recruited to membranes during the canonical autophagy process?

    <p>ATG16L1 via the FBD</p> Signup and view all the answers

    What is the significance of LC3 lipidation in autophagy?

    <p>It serves to conjugate LC3 to the isolation membrane</p> Signup and view all the answers

    Which protein complex involves recruitment during the initiation of autophagy?

    <p>The ULK1 complex</p> Signup and view all the answers

    What is an alternative role of ATG16L1 in non-canonical pathways?

    <p>Recruitment via its C-terminal WD40 domain</p> Signup and view all the answers

    What happens to mitochondria during the process described?

    <p>They are sequestered by autophagosomes</p> Signup and view all the answers

    Which membrane structure is represented in green in the 3D rendering?

    <p>Autophagosomal compartment</p> Signup and view all the answers

    Which protein is NOT part of the ULK1 complex mentioned?

    <p>LC3</p> Signup and view all the answers

    Study Notes

    LC3-associated Phagocytosis (LAP)

    • LAP uses a portion of the canonical autophagy machinery
    • Characterized by the conjugation of LC3 family proteins to phagosome membranes
    • Cargos: pathogens, dying cells, soluble ligands, protein aggregates
    • Involved in immune activation and inflammatory responses

    LAP Pathway

    • Not dependent on the AMPK–mTORC1–ULK1 axis
    • Not responsive to nutrient status or intracellular stress sensing
    • Activating stimulus from the cell exterior: ligands, pathogens, dying cells, immune complexes
    • Requires the PI3KC3 complex composed of VPS34, VPS15, BECN1, ATG14L, UVRAG, RUBCN
    • ULK complex (ULK1, FIP200, ATG13, ATG101) is dispensable for LAP

    Autophagosome Formation and Expansion

    • Atg8s are dispensable for autophagosome formation but regulate autophagosome expansion
    • Hexa KO cell deficient for all ATG8/GABARAP members: 3D rendering of reconstructed autophagosomal compartment (green) and sequestered mitochondrion (red)

    Non-Canonical Functions of ATG16L1

    • Model for the recruitment of ATG16L1 to membranes:
      • Induction of LC3 lipidation during autophagy depends on the ULK1 complex subunit FIP200 and WIPI2
      • Recruitment of ATG16L1 to the site of autophagosome formation via the FBD, leading to LC3 conjugation to the isolation membrane
      • During autophagy-unrelated, non-canonical pathways involving LC3 lipidation, ATG16L1 is recruited via its C-terminal WD40 domain and promotes the lipidation of LC3 to single membranes

    Autophagy Receptors

    • Autophagy receptors: p62, NBR1 (neighbor of BRCA1 gene 1), etc.
    • Functions of autophagy receptors and adaptors in selective autophagy
    • Selective recruitment of phagophores to cargos through the interaction of autophagy receptors with LC3II
    • Selective autophagy types and corresponding receptors
    • Regulatory modifications reported for selective autophagy receptors

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    Description

    LAP is a process that uses autophagy machinery to engulf and remove pathogens, dying cells, and other cargos, playing a role in immune activation and inflammation. It is activated by external stimuli and does not respond to nutrient status or intracellular stress.

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