Rab39a interacts with phosphatidylinositol 3-kinase and negatively regulates autophagy induced by lipopolysaccharide stimulation in macrophages

Rab39a has pleiotropic functions in phagosome maturation, inflammatory activation and neuritogenesis. Here, we characterized Rab39a function in membrane trafficking of phagocytosis and autophagy induction in macrophages. Rab39a localized to the periphery of LAMP2-positive vesicles and showed the sim...

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Bibliographic Details
Published in:PloS one 2013-12, Vol.8 (12), p.e83324-e83324
Main Authors: Seto, Shintaro, Sugaya, Keiko, Tsujimura, Kunio, Nagata, Toshi, Horii, Toshinobu, Koide, Yukio
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Amino acids
Analysis
Animals
Augmentation
Autophagy
Autophagy - drug effects
Autophagy - physiology
Axonogenesis
Bone marrow
Cell activation
Cell death
Cell Line
Cytokines
Depletion
Enzyme inhibitors
Humans
Immunoglobulins
Immunoprecipitation
Infectious diseases
Inflammation
Kinetics
Lipopolysaccharides
Lipopolysaccharides - pharmacology
Localization
Lysosomal Membrane Proteins - genetics
Lysosomal Membrane Proteins - metabolism
Macrophages
Macrophages - cytology
Macrophages - metabolism
Medicine
Membrane trafficking
Mice
Mice, Knockout
Microscopy
Mitogens
Phagocytosis
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Phospholipids
Protein Binding - drug effects
Protein Binding - physiology
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
Recovery (Medical)
Sepsis
Stimulation
Trends
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Summary:Rab39a has pleiotropic functions in phagosome maturation, inflammatory activation and neuritogenesis. Here, we characterized Rab39a function in membrane trafficking of phagocytosis and autophagy induction in macrophages. Rab39a localized to the periphery of LAMP2-positive vesicles and showed the similar kinetics on the phagosome to that of LAMP1. The depletion of Rab39a did not influence the localization of LAMP2 to the phagosome, but it augments the autophagosome formation and LC3 processing by lipopolysaccharide (LPS) stimulation. The augmentation of autophagosome formation in Rab39a-knockdown macrophages was suppressed by Atg5 depletion or an inhibitor for phosphatidylinostol 3-kinase (PI3K). Immunoprecipitation analysis revealed that Rab39a interacts with PI3K and that the amino acid residues from 34(th) to 41(st) in Rab39a were indispensable for this interaction. These results suggest that Rab39a negatively regulates the LPS-induced autophagy in macrophages.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0083324