• Vesicle Prep Pro

    有機溶媒フリーで巨大単層ベシクル(GUV)を自動調製可能な市場初のシステム
  • Vesicle Prep Pro

    均一サイズのリポソームを自動調製 - 多様なアプリケーション

2020 - Membrane characteristics tune activities of endosomal and autophagic human VPS34 complexes

icon vpp   Vesicle Prep Pro publication in eLife (2020)

Authors:
Ohashi Y., Tremel S., Masson G.R., McGinney L., Boulanger J., Rostislavleva K., Johnson C.M., Niewczas I., Clark J., Williams R.J.

Journal:
eLife (2020) 9:e58281  doi: 10.7554/eLife.58281


Abstract:

The lipid kinase VPS34 orchestrates diverse processes, including autophagy, endocytic sorting, phagocytosis, anabolic responses and cell division. VPS34 forms various complexes that help adapt it to specific pathways, with complexes I and II being the most prominent ones. We found that physicochemical properties of membranes strongly modulate VPS34 activity. Greater unsaturation of both substrate and non-substrate lipids, negative charge and curvature activate VPS34 complexes, adapting them to their cellular compartments. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) of complexes I and II on membranes elucidated structural determinants that enable them to bind membranes. Among these are the Barkor/ATG14L autophagosome targeting sequence (BATS), which makes autophagy-specific complex I more active than the endocytic complex II, and the Beclin1 BARA domain. Interestingly, even though Beclin1 BARA is common to both complexes, its membrane-interacting loops are critical for complex II, but have only a minor role for complex I.


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