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J Biol Chem. 2017 Apr 28. pii: jbc.M117.792747. doi: 10.1074/jbc.M117.792747. [Epub ahead of print]
Endophilin B2 facilitates endosome maturation in response to growth factor stimulation, autophagy induction, and influenza A virus infection.
Serfass JM1, Takahashi Y1, Zhou Z2, Imamura Kawasawa Y1, Liu Y1, Tsotakos N1, Young MM1, Tang Z1, Yang L1, Atkinson JM1, Chroneos ZC1, Wang HG3.
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Abstract
Endocytosis, and the subsequent trafficking of endosomes, requires dynamic physical alterations in membrane shape that are mediated in part by endophilin proteins. The endophilin B family of proteins contains an N-terminal Bin/Amphiphysin/Rvs (N-BAR) domain that induces membrane curvature to regulate intracellular membrane dynamics. While endophilin B1 (SH3GLB1/Bif-1) is known to be involved in a number of cellular processes, including apoptosis, autophagy and endocytosis, the cellular function of endophilin B2 (SH3GLB2) is not well understood. In this study, we used genetic approaches that revealed that endophilin B2 is not required for embryonic development in vivo, but that endophilin B2 deficiency impairs endosomal trafficking in vitro as evidenced by suppressed endosome acidification, EGFR degradation, autophagic flux, and influenza A viral RNA nuclear entry and replication. Mechanistically, although the loss of endophilin B2 did not affect endocytic internalization and lysosomal function, endophilin B2 appeared to regulate the trafficking of endocytic vesicles and autophagosomes to late endosomes or lysosomes. Moreover, we also found that despite having an intracellular localization and tissue distribution similar to endophilin B1, endophilin B2 is dispensable for mitochondrial apoptosis. Taken together, our findings suggest that endophilin B2 positively regulates the endocytic pathway in response to growth factor signaling, autophagy induction, and viral entry.
Copyright ? 2017, The American Society for Biochemistry and Molecular Biology.
KEYWORDS:
EGFR degradation; Endophilin B2; SH3GLB2; autophagy; endocytosis; endosome maturation; influenza; intracellular trafficking; virus entry
PMID: 28455444 DOI: 10.1074/jbc.M117.792747
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Endophilin B2 facilitates endosome maturation in response to growth factor stimulation, autophagy induction, and influenza A virus infection.
Serfass JM1, Takahashi Y1, Zhou Z2, Imamura Kawasawa Y1, Liu Y1, Tsotakos N1, Young MM1, Tang Z1, Yang L1, Atkinson JM1, Chroneos ZC1, Wang HG3.
Author information
Abstract
Endocytosis, and the subsequent trafficking of endosomes, requires dynamic physical alterations in membrane shape that are mediated in part by endophilin proteins. The endophilin B family of proteins contains an N-terminal Bin/Amphiphysin/Rvs (N-BAR) domain that induces membrane curvature to regulate intracellular membrane dynamics. While endophilin B1 (SH3GLB1/Bif-1) is known to be involved in a number of cellular processes, including apoptosis, autophagy and endocytosis, the cellular function of endophilin B2 (SH3GLB2) is not well understood. In this study, we used genetic approaches that revealed that endophilin B2 is not required for embryonic development in vivo, but that endophilin B2 deficiency impairs endosomal trafficking in vitro as evidenced by suppressed endosome acidification, EGFR degradation, autophagic flux, and influenza A viral RNA nuclear entry and replication. Mechanistically, although the loss of endophilin B2 did not affect endocytic internalization and lysosomal function, endophilin B2 appeared to regulate the trafficking of endocytic vesicles and autophagosomes to late endosomes or lysosomes. Moreover, we also found that despite having an intracellular localization and tissue distribution similar to endophilin B1, endophilin B2 is dispensable for mitochondrial apoptosis. Taken together, our findings suggest that endophilin B2 positively regulates the endocytic pathway in response to growth factor signaling, autophagy induction, and viral entry.
Copyright ? 2017, The American Society for Biochemistry and Molecular Biology.
KEYWORDS:
EGFR degradation; Endophilin B2; SH3GLB2; autophagy; endocytosis; endosome maturation; influenza; intracellular trafficking; virus entry
PMID: 28455444 DOI: 10.1074/jbc.M117.792747
Free full text