Location: Home \ NEWS\ In The Spotlight

The key role of RAB2 in autophagic structures identified

[Source]: [Author]: [Date]: 2019-04-17[Views]: 1425

Autophagy is a lysosomal degradative pathway essential to development and homeostasis. The deregulation of autophagy is tightly associated with a variety of human diseases. Studies have shown that the biogenesis of autophagosomes needs membranes from multiple sources, including ER, the Golgi network, mitochondria, the endosomes and ER-Golgi intermediate. It remains elusive as to how the membranes from different sources are directionally delivered for the formation and expansion of a phagophore, which eventually seals to form an autophagosome.

Due to its widespread distribution and distinctive transmembrane structure, ATG9 is perceived as an eligible candidate to deliver membranes from different sources. However, it remains ambiguous how Golgi-derived ATG9-positive (ATG9+) vesicles are transported and integrated into early autophagic structures in mammalian cells.

Relevant research conducted by SUN Qiming and his team is published online in an article entitled “RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells” in the journal of Autophagy.

In their research, SUN Qiming et al. discover that RAB2 connects the Golgi network with the autophagy pathway by delivering membranes and by sequentially engaging distinct autophagy machineries. In unstressed cells, RAB2 resides primarily in the Golgi apparatus, as evidenced by its interaction and colocalization with GOLGA2/GM130. Equally importantly, autophagy stimuli dissociate RAB2 from GOLGA2 to interact with ULK1 complex, which facilitates the recruitment of ULK1 complex to form phagophores. It is intriguing that RAB2 appears to modulate ULK1 kinase activity to propagate signals for the formation of autophagosome. Subsequently, RAB2 switches to interact with autophagosomal RUBCNL/PACER and STX17 to further specify the recruitment of theHOPS complex for the formationof autolysosome.

This study presents a multivalent pathway in bulk autophagy regulation and provides insights into how the Golgi apparatus contributes to the formation of different autophagic structures.