Most functions of eukaryotic cells are controlled by cellular membranes, which are not static entities but undergo frequent budding, fission, fusion, and sculpting reactions collectively referred to as membrane dynamics. Consequently, regulation of membrane dynamics is crucial for cellular functions. A key mechanism in such regulation is the reversible recruitment of cytosolic proteins or protein complexes to specific membranes at specific time points. To a large extent this recruitment is orchestrated by phosphorylated derivatives of the membrane lipid phosphatidylinositol, known as phosphoinositides. The seven phosphoinositides found in nature localize to distinct membrane domains and recruit distinct effectors, thereby contributing strongly to the maintenance of membrane identity. Many of the phosphoinositide effectors are proteins that control membrane dynamics, and in this review we discuss the functions of phosphoinositides in membrane dynamics during exocytosis, endocytosis, autophagy, cell division, cell migration, and epithelial cell polarity, with emphasis on protein effectors that are recruited by specific phosphoinositides during these processes.

2020) ESCRT-mediated phagophore sealing during mitophagy, Autophagy, 16:5, 826-841, ABSTRACT Inactivation of the endosomal sorting complex required for transport (ESCRT) machinery has been reported to cause autophagic defects, but the exact functions of ESCRT proteins in macroautophagy/ autophagy remain incompletely understood. Using live-cell fluorescence microscopy we found that the filament-forming ESCRT-III subunit CHMP4B was recruited transiently to nascent autophagosomes during starvation-induced autophagy and mitophagy, with residence times of about 1 and 2 min, respectively. Correlative light microscopy and electron tomography revealed CHMP4B recruitment at a late step in mitophagosome formation. The autophagosomal dwell time of CHMP4B was strongly increased by depletion of the regulatory ESCRT-III subunit CHMP2A. Using a novel optogenetic closure assay we observed that depletion of CHMP2A inhibited phagophore sealing during mitophagy. Consistent with this, depletion of CHMP2A and other ESCRT-III subunits inhibited both PRKN/PARKINdependent and -independent mitophagy. We conclude that the ESCRT machinery mediates phagophore closure, and that this is essential for mitophagic flux.

STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum and regulate store-operated Ca2+ entry. STIM2 mediates cAMP/PKA-dependent phosphorylation of the AMPA receptor subunit GluA1 in excitatory neurons. In addition, STIM2 promotes cAMP-dependent surface delivery of GluA1.

Highlights d Drosophila ALIX is recruited to the midbody via its V-domain d Centralspindlin/Pavarotti interacts with and recruits ALIX to the midbody d ALIX interacts with Pavarotti via a conserved hydrophobic pocket in the V-domain d Pavarotti recruits ALIX via a mechanism analogous to virus budding