Rabin8 suppresses autophagosome formation independently of its guanine nucleotide-exchange activity towards Rab8

Journal of Biochemistry
Yuta AmagaiKensaku Mizuno

Abstract

Macroautophagy is a bulk degradation system conserved from yeast to human. In budding yeast, the guanine nucleotide-exchange factor (GEF) Sec2p is required for autophagy. We examined the role of Rabin8 (a mammalian ortholog of Sec2p) with Rab8-GEF activity in autophagy in mammalian cells. Unexpectedly, depletion of Rabin8 promoted nutrient starvation-induced autophagosome formation, indicating that Rabin8 suppresses autophagosome formation. Depletion of Rab8 did not affect autophagosome formation, and expression of a Rabin8 GEF-domain mutant reverted the Rabin8 depletion-induced increase in autophagosomes, indicating that Rabin8 suppresses autophagosome formation independently of its Rab8-GEF activity. Nuclear Dbf2-related (NDR) kinases phosphorylate Rabin8 at Ser-272. The non-phosphorylatable Rabin8-S272A mutant did not revert the Rabin8 depletion-induced increase in autophagosomes, suggesting that Ser-272 phosphorylation of Rabin8 is involved in its suppressive function in autophagy. Depletion of NDR kinases enhanced autophagosome formation and reduced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) activity, suggesting that NDR kinases suppress autophagosome formation by increasing mTORC1 activity, in addition t...Continue Reading

References

Apr 4, 2000·The Journal of Cell Biology·N B ElkindP J Novick
Sep 11, 2002·Molecular Biology of the Cell·Katarina HattulaJohan Peränen
Apr 14, 2006·Molecular Biology of the Cell·Martina MedkovaPeter Novick
Jul 25, 2007·The Journal of Cell Biology·Shin-Ichiro YoshimuraFrancis A Barr
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
Feb 13, 2009·Molecular Biology of the Cell·Nao HosokawaNoboru Mizushima
Feb 20, 2009·Molecular Biology of the Cell·Chang Hwa JungDo-Hyung Kim
Mar 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andreas KnödlerWei Guo
May 7, 2010·Molecular Biology of the Cell·Jiefei GengDaniel J Klionsky
Jun 22, 2010·Nature·Christian BehrendsJ Wade Harper
Oct 5, 2010·Nature Cell Biology·David M BryantKeith E Mostov
Oct 12, 2010·Autophagy·Nicholas T KtistakisJoshua Long
Jan 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christopher J WestlakePeter K Jackson
Jul 26, 2011·Cell·Usha NairDaniel J Klionsky
Jul 26, 2011·Cell·Kevin MoreauDavid C Rubinsztein
Mar 22, 2012·The Journal of Biological Chemistry·Shanshan FengWei Guo
Feb 8, 2013·Molecular Biology of the Cell·Puneet KhandelwalGerard Apodaca
Jun 4, 2013·Seminars in Cancer Biology·Martina WirthSharon A Tooze
Oct 4, 2013·Nature·Olatz PampliegaAna Maria Cuervo
Nov 10, 2013·Nature Reviews. Molecular Cell Biology·Christopher A LambSharon A Tooze

❮ Previous
Next ❯

Citations

May 14, 2016·Molecular Biology of the Cell·Yuta Homma, Mitsunori Fukuda
Nov 29, 2017·Journal of Cell Science·Kengo TakahashiKensaku Mizuno
Oct 7, 2020·Biomarkers in Medicine·Parisa M DanaZatollah Asemi
Nov 6, 2020·Reproductive Biology and Endocrinology : RB&E·Yalan MaLianwen Zheng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.