| 2007 |
Yeast Ist1 has a dual role in regulating Vps4: it localizes to the ESCRT machinery via Did2 where it positively recruits Vps4, and it also negatively regulates Vps4 by forming an Ist1-Vps4 heterodimer in which Vps4 cannot bind the ESCRT machinery. |
Genetic and biochemical analysis in S. cerevisiae, including co-immunoprecipitation and mutant analysis |
Molecular biology of the cell |
High |
18032582
|
| 2007 |
Yeast Ist1 forms a specific physical complex with Did2, and both Ist1-Did2 and Vta1-Vps60 compose two independent functional units that modulate late steps in MVB sorting; Ist1 endosomal recruitment depends on ESCRT-III. |
Synthetic genetic analysis (double mutants), co-immunoprecipitation, endosomal localization assays in S. cerevisiae |
Molecular biology of the cell |
High |
18032584
|
| 2009 |
Human IST1 is required for efficient cytokinetic abscission in HeLa cells; IST1 contains two distinct MIT-interacting motifs (MIM1 and MIM2) at its C-terminus that bind different grooves of the VPS4 MIT domain; IST1 and CHMP1 co-recruit VPS4 to the midbody, and depletion of either blocks VPS4 recruitment and abscission. IST1 depletion does not inhibit HIV-1 budding. |
RNAi knockdown with cytokinesis phenotype readout, NMR spectroscopy, mutagenesis, midbody localization by immunofluorescence, viral budding assay |
Molecular biology of the cell |
High |
19129479
|
| 2009 |
The crystal structure of the Ist1 N-terminal domain reveals an ESCRT-III subunit-like fold, identifying Ist1 as a divergent ESCRT-III family member; Ist1NTD specifically binds the Did2 C-terminal MIM1 via a novel MIM-binding structural motif, revealing a mechanism for intermolecular ESCRT-III subunit association. |
X-ray crystallography of Ist1NTD alone and co-crystallized with Did2 fragment; binding assays |
Molecular biology of the cell |
High |
19477918
|
| 2010 |
The SPG20 protein spartin is recruited to the midbody through its MIT domain binding to IST1 (but not other CHMP proteins); Ist1 depletion significantly reduces spartin at midbodies; a structure-based mutation (F24D) in spartin MIT domain blocks spartin-IST1 interaction and prevents midbody localization, acting as dominant-negative to impair cytokinesis. |
Yeast two-hybrid, surface plasmon resonance, siRNA knockdown, immunofluorescence co-localization, dominant-negative rescue experiments |
Molecular biology of the cell |
High |
20719964
|
| 2010 |
Human IST1 interacts with the tandem MIT domains of calpain 7 via both MIM1 and MIM2, and the IST1 MIM (GST-MIM fusion) enhances autolytic activity of purified calpain 7 in vitro; autolysis requires the catalytic Cys290 and is abolished by N-ethylmaleimide. |
GST pulldown, co-immunoprecipitation with deletion/point mutants, in vitro autolysis assay with purified proteins, catalytic-dead mutant (C290S) |
The FEBS journal |
Medium |
20849418
|
| 2011 |
Calpain-7 binds CHMP1B at its second α-helical region (not the canonical MIM1 region), and forms a ternary complex with IST1; coexpression of CHMP1B and IST1 enhances calpain-7 autolysis in cells; ternary complex formation increases calpain-7 recruitment to membrane/organelle fractions. |
Co-immunoprecipitation with deletion mutants, in vitro pulldown, cell-based autolysis assay (HEK293T), subcellular fractionation |
Journal of biochemistry |
Medium |
21616915
|
| 2013 |
Mammalian IST1 possesses a distinctive Met-Pro repeat sequence that is essential for Ca2+-dependent interaction with the EF-hand Ca2+-binding protein ALG-2; this interaction is enhanced by co-expression with CHMP1 proteins; IST1 binds ALG-2 by a different mode than other known ALG-2-interacting proteins. |
Far-Western blotting with biotinylated ALG-2, pulldown assays with deletion mutants of IST1 and GST-ALG-2 mutants |
Bioscience, biotechnology, and biochemistry |
Medium |
23649269
|
| 2015 |
Crystal structures of IST1 MIM complexed with MIT domains of VPS4, LIP5, and Spartin reveal two distinct binding mechanisms (MIM1 mode vs. MIM3 mode); two phenylalanine residues in IST1 MIM discriminate MIM1 vs. MIM3 binding; structural features in both MIT and MIM determine specificity. |
X-ray crystallography of three binary complexes, mutagenesis validating key residues |
The Journal of biological chemistry |
High |
25657007
|
| 2015 |
Ist1 inhibition of Vps4 ATPase activity involves both the MIM and a conserved ELYC surface; an open conformation of the Ist1 core together with MIM interaction stimulates Vps4; binding of Did2 converts Ist1 from a Vps4 inhibitor to a stimulator, and this shift corresponds to altered ESCRT-III disassembly in vitro. |
ATPase activity assays, in vitro ESCRT-III disassembly assay, mutagenesis of Ist1 conformational elements |
The Journal of biological chemistry |
High |
26515066
|
| 2019 |
IST1 facilitates association of CHMP2B and CHMP4B/SNF7-2 to form the ESCRT-III complex required for autophagosome-lysosome fusion; lack of IST1 impedes ESCRT-III complex formation and blocks autophagosome-lysosome fusion; MAPT/tau accumulation suppresses IST1 transcription via the ANP32A-INHAT pathway. |
Co-immunoprecipitation, AAV-mediated overexpression/knockdown in transgenic mice, autophagy flux assays (LC3-II, p62, autophagosome imaging) |
Autophagy |
Medium |
31223056
|
| 2022 |
In yeast, Ist1 is ubiquitinated, and this ubiquitination is required for proper endosomal recruitment of Ist1 and for recycling of nutrient transporters from endosomes back to the plasma membrane; the AAA-ATPase Cdc48 and its adaptor Npl4 are required for recycling, potentially through regulation of ubiquitinated Ist1. |
Ubiquitination assays, genetic mutant analysis, fluorescence microscopy of cargo recycling in S. cerevisiae |
The Journal of cell biology |
Medium |
36125415
|
| 2023 |
Human IST1, together with its binding partner CHMP1B, contributes to scission of early endosomal carriers; depleting IST1 impairs transferrin receptor delivery from early/sorting endosomes to the endocytic recycling compartment and impairs mannose-6-phosphate receptor export; IST1 interacts with the MIT domain-containing sorting nexin SNX15 on endosomes; SNX15 and CHMP1B alternately recruit IST1 to a clathrin-containing subdomain or the base of endosomal tubules. |
siRNA depletion, live-cell microscopy, kinetic and spatial cargo tracking, co-immunoprecipitation with SNX15 |
Traffic (Copenhagen, Denmark) |
Medium |
37926552
|
| 2023 |
CAPN7 (Calpain-7) tandem MIT domains bind simultaneously to two distinct MIM motifs on IST1; structure-guided point mutations in either CAPN7 MIT domain disrupt IST1 binding in vitro and in cells; the CAPN7-IST1 interaction is required for CAPN7 recruitment to midbodies, efficient cytokinetic abscission, and NoCut checkpoint arrest; CAPN7 proteolytic activity is also required for abscission and checkpoint maintenance. |
X-ray crystallography of CAPN7 MIT-IST1 MIM complexes, mutagenesis, co-immunoprecipitation, siRNA depletion/rescue experiments, abscission and checkpoint assays |
eLife |
High |
37772788
|
| 2024 |
A pseudonatural product compound specifically disrupts the IST1-CHMP1B interaction, inhibiting IST1-CHMP1B copolymer formation required for normal-topology membrane scission; this inhibition rapidly blocks transferrin receptor recycling, causing accumulation in stalled sorting endosomes; stalled endosomes become decorated by lipidated LC3, linking noncanonical LC3 lipidation to IST1-CHMP1B complex disruption. The compound has no impact on cytokinesis, MVB sorting, or extracellular vesicle biogenesis. |
Chemical inhibitor treatment, transferrin recycling assay, LC3 lipidation assay, live-cell imaging, biogenesis assays for MVBs and extracellular vesicles |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
38635626
|
| 2025 |
Endogenous IST1 exists in at least two distinct pools on endosomes (one transient, one relatively stable); upon growth factor stimulation, the stable pool becomes more mobile and the transient pool accumulates more rapidly; ESCRT-III dynamics are distinct from those of other ESCRT complexes, and an intrinsic amount of time is required for ESCRT-mediated ILV biogenesis. |
CRISPR tagging of endogenous Ist1, high-speed live-cell imaging, fluorescence microscopy |
The Journal of cell biology |
Medium |
41060239
|
| 2025 |
DeSUMOylated Spastin (Spastin-K427R) exhibits enhanced binding to IST1 compared to wild-type Spastin; co-overexpression of IST1 with Spastin enhances synaptic transmission and spine maturation; IST1 knockdown reduces GluA1 surface levels and abolishes Spastin's effects on AMPAR recycling, indicating IST1 is a key mediator of Spastin-dependent AMPAR endosomal recycling. |
Co-immunoprecipitation, siRNA knockdown, overexpression, immunofluorescence, electrophysiology (mEPSC recording) |
Molecular neurobiology |
Medium |
41296224
|
| 2025 |
In mammalian cytokinetic abscission, CHMP2A knockout causes minimal disruption to IST1 and CHMP2B localization at the abscission site, while CHMP4B, CHMP3, and CHMP1B show progressively severe organization defects, supporting a hierarchical ESCRT-III assembly model in which IST1 is among the least dependent on CHMP2A. |
CHMP2A knockout, live-cell imaging, structured illumination microscopy (SIM), correlative light-electron microscopy (CLEM) |
bioRxivpreprint |
Low |
bio_10.1101_2025.06.24.661003
|