| 2007 |
Exo70 C-terminal Domain D directly interacts with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane, and this interaction (but not its interaction with Rho3) is essential for membrane association of the exocyst complex and tethering of post-Golgi secretory vesicles. |
Direct lipid-binding assays, key residue mutagenesis, genetic and cell biological analyses in yeast |
The EMBO journal |
High |
17717527
|
| 2004 |
Exo70p (and Sec3p) are stable plasma membrane components of the exocyst, whereas the other six subunits arrive on secretory vesicles; exocyst assembly occurs when vesicle-borne subunits join Exo70p and Sec3p at the plasma membrane to tether vesicles to exocytic sites. |
FRAP (photobleaching recovery), actin disruption, immunogold EM, epifluorescence video microscopy in yeast |
The Journal of cell biology |
High |
15583031
|
| 1999 |
Exo70 interacts with the yeast GTPase Rho3 in a GTP-dependent manner; this interaction requires the Rho3 effector domain and was demonstrated with purified proteins in vitro. Overlapping subcellular localization of Rho3 and Exo70 was confirmed by immunofluorescence. |
Yeast two-hybrid screen, purified protein binding assay, indirect immunofluorescence |
Molecular and cellular biology |
High |
10207081
|
| 2006 |
Human Exo70 directly interacts with the Arp2/3 complex, and this interaction is regulated by EGF signaling. Inhibition of Exo70 by RNAi or antibody microinjection blocks actin-based membrane protrusion formation and impairs cell motility. |
Co-immunoprecipitation, RNAi knockdown, antibody microinjection, live cell imaging |
Nature cell biology |
High |
17086175
|
| 2005 |
Crystal structure of yeast Exo70p determined at 2.0 Å resolution reveals an ~160 Å rod composed of contiguous α-helical bundles (novel fold). Structural analysis combined with binding experiments shows Exo70p binds Rho3p in a GTP-dependent manner (Kd ~70 µM) and interacts with other exocyst subunits. |
X-ray crystallography (2.0 Å), equilibrium binding assay |
Nature structural & molecular biology |
High |
16249794
|
| 2005 |
Crystal structure of S. cerevisiae Exo70p determined at 3.5 Å resolution shows an extended rod (~155 Å) composed principally of α-helices with a novel fold; Exo70p binds Rho3p GTPase in a GTP-dependent manner. |
X-ray crystallography (3.5 Å), GTPase binding assay |
Journal of molecular biology |
High |
16359701
|
| 2012 |
ERK1/2 directly phosphorylate Exo70 in response to EGF signaling, enhancing Exo70 binding to other exocyst subunits and promoting exocyst complex assembly. Blocking ERK1/2 signaling or expressing an ERK1/2-phosphorylation-deficient Exo70 mutant inhibits exocytosis, matrix metalloproteinase secretion, and invadopodia formation in tumor cells. |
In vitro kinase assay, phosphorylation-deficient mutant expression, chemical inhibitor treatment, exocytosis assay, Co-IP |
Developmental cell |
High |
22595671
|
| 2013 |
Exo70 generates negative membrane curvature through an oligomerization-based mechanism, inducing tubular membrane invaginations in synthetic vesicles in vitro and protrusions on cell surfaces. This membrane-deformation function requires specific residues identified by mutagenesis and is necessary for protrusion formation and directional cell migration. |
In vitro membrane tubulation assay with synthetic vesicles, Exo70 mutant analysis, molecular dynamics simulation, live cell imaging |
Developmental cell |
High |
23948253
|
| 2013 |
Exo70 undergoes isoform switching regulated by the splicing factor ESRP1 during EMT. The mesenchymal isoform (but not the epithelial isoform) interacts with the Arp2/3 complex and stimulates actin polymerization to drive tumor invasion. |
Isoform-specific expression constructs, Co-IP with Arp2/3, RNAi, in vitro actin polymerization assay, invasion assays, mouse tumor metastasis model |
Developmental cell |
High |
24331928
|
| 2012 |
Exo70 functions as a kinetic activator of the Arp2/3 complex, promoting actin filament nucleation and branching by facilitating interaction of Arp2/3 with WAVE2. This stimulatory activity is required for lamellipodia formation and maintaining directional persistence during cell migration. |
In vitro actin polymerization assay, TIRF microscopy, Co-IP, RNAi knockdown, live cell migration assay |
Current biology : CB |
High |
22748316
|
| 2009 |
The TC10-Exo70 complex is required for IGF-1-stimulated membrane expansion and axonal specification in hippocampal neurons. IGF-1 activates TC10, which triggers translocation of Exo70 to the plasma membrane in the distal axon and growth cone; TC10 and Exo70 function are necessary for new membrane addition and polarized insertion of IGF-1 receptor. |
Dominant-negative and siRNA knockdown of TC10 and Exo70, plasma membrane fractionation, immunofluorescence, live imaging in cultured neurons and isolated growth cones |
The Journal of neuroscience |
High |
19846717
|
| 2020 |
ULK1 directly phosphorylates Exo70, inhibiting Exo70 homo-oligomerization and its assembly into the exocyst complex, thereby suppressing cell protrusion formation, MMP secretion, and cancer cell invasion. ERK1/2 phosphorylation of Exo70 counteracts ULK1 phosphorylation upon growth factor stimulation. |
In vitro kinase assay, phosphorylation-deficient and phospho-mimetic mutants, Co-IP for complex assembly, invasion and migration assays |
Nature communications |
High |
31913283
|
| 2007 |
Exo70p in yeast selectively mediates secretion of Bgl2p vesicles (one class of post-Golgi vesicles) primarily during early stages of the cell cycle; this selective block does not affect vesicle formation or sorting but occurs at the tethering/fusion step. |
Genetic analysis of exo70 mutants, vesicle accumulation assays, cargo-specific secretion assays in yeast |
The Journal of cell biology |
High |
17339375
|
| 2005 |
Exo70 interacts with BIG2 (a brefeldin A-inhibited GEF for ARFs); the interaction involves the N-terminal segment of BIG2 (aa 1–643). Both BIG2 and Exo70 colocalize at Golgi membranes and the MTOC/centrosome in HepG2 cells. |
Yeast two-hybrid screen, co-immunoprecipitation of in vitro-translated proteins, immunofluorescence microscopy, centrosome purification |
PNAS |
Medium |
15705715
|
| 2007 |
Exo70 interacts with Snapin via Exo70's N-terminal coiled-coil domain and Snapin's C-terminal helical region; Exo70 competes with SNAP23 for Snapin binding. Depletion of Snapin by RNAi inhibits insulin-stimulated glucose uptake in adipocytes, implicating this interaction in GLUT4 vesicle trafficking. |
Co-IP, domain mapping, competition assay, RNAi knockdown, glucose uptake assay in adipocytes |
The Journal of biological chemistry |
Medium |
17947242
|
| 2011 |
Exo70 directly interacts with type Iγ PIP5-kinase (PIPKIγ), which mediates association of E-cadherin with Exo70 and targets Exo70 to adherens junctions. Exo70 is necessary for E-cadherin clustering and extension of nascent E-cadherin adhesions; PIPKIγ-generated PI(4,5)P2 recruits Exo70 to nascent E-cadherin junctions. |
Co-IP, pulldown, RNAi knockdown, confocal microscopy, PI(4,5)P2 localization assay |
Molecular biology of the cell |
Medium |
22049025
|
| 2009 |
Exo70 mediates insulin-stimulated tethering of GLUT4 vesicles to the plasma membrane in primary rat adipocytes; an Exo70-N mutant induces insulin-independent tethering but not fusion, indicating that Exo70-mediated tethering is upstream of and separable from the insulin-regulated fusion step. |
TIRF microscopy for single vesicle tracking, Exo70 overexpression and dominant-negative mutant in primary adipocytes |
The Journal of biological chemistry |
Medium |
19155211
|
| 2019 |
Inducible knockout of Exoc7 in adipocytes markedly inhibits insulin-stimulated GLUT4 exocytosis without affecting insulin signaling, demonstrating a critical and specific role for the exocyst (via Exo70) in GLUT4 vesicle exocytosis downstream of insulin receptor signaling. |
Inducible CRISPR/Cas9 knockout in adipocytes, GLUT4 translocation assay, insulin signaling assessment |
The Journal of biological chemistry |
High |
31740584
|
| 2008 |
Domain C of yeast Exo70p (while not essential for growth) is required for actin-independent localization of Exo70p to exocytic sites and for assembly of Sec5p and Sec6p into the exocyst. Loss of domain C causes synthetic lethality with secretory mutations analogous to loss of Sec3p's Cdc42/Rho1-binding domain. |
Domain deletion analysis, genetic epistasis (synthetic lethality), exocyst subunit assembly assay, localization microscopy in yeast |
Molecular biology of the cell |
High |
18946089
|
| 2014 |
Exo70p directly and specifically binds the polarity scaffold Bem1p via multiple domains of both proteins. Mutations disrupting Exo70p-Bem1p interaction abolish actin-independent localization of Exo70p. Actin-independent localization requires a synergistic interaction with PI(4,5)P2. |
Yeast two-hybrid, purified protein pulldown, domain deletion mutants, genetic epistasis, localization microscopy |
The Journal of cell biology |
High |
25313406
|
| 2011 |
Exo70 interacts directly with SNEV (hPrp19/hPso4) via its N-terminal 100 amino acids and shuttles to the nucleus where it associates with the spliceosome. Exo70 influences pre-mRNA splicing in vitro and modulates splicing of its own pre-mRNA in vivo. |
Co-IP, nuclear fractionation, in vitro splicing assay, domain mapping, in vivo splicing reporter |
The Biochemical journal |
Medium |
21639856
|
| 2007 |
NGF induces interaction of activated TC10 with Exo70 in PC12 cells (shown by FRET-FLIM). The Exo70-TC10 complex locally antagonizes Cdc42-mediated activation of N-WASP at membrane protrusions to regulate the form of membrane outgrowth during neurite formation. |
FRET-FLIM imaging, dominant-negative mutants, siRNA knockdown, N-WASP activation biosensor |
Journal of cell science |
Medium |
17635999
|
| 2009 |
Exo70 recruits nucleoporin Nup62 to the leading edge of migrating cells through direct binding involving the N-terminal domain of Exo70 and the coiled-coil domain of Nup62. RNAi silencing of Nup62 significantly reduces cell migration; removal of the Exo70-binding domain of Nup62 prevents its leading edge localization. |
Co-IP, domain mapping pulldown, RNAi knockdown, confocal microscopy |
Traffic (Copenhagen, Denmark) |
Medium |
19552648
|
| 2013 |
GTP hydrolysis of vesicular TC10 near the plasma membrane releases Exo70, accelerating vesicle fusion and promoting neurite outgrowth. Constitutively active TC10 cannot rescue neurite outgrowth defects caused by TC10 depletion, indicating that the GTPase cycle is required. |
FRET biosensors for TC10 activity, live cell imaging of vesicle fusion, TC10 knockdown and rescue experiments in neuronal cells |
PloS one |
Medium |
24223996
|
| 2020 |
Loss of exoc7 in zebrafish causes microcephaly, and EXOC7 partial loss-of-function variants in humans cause a recessive disorder of cerebral cortex development with brain atrophy, seizures, and in severe cases microcephaly; EXOC7 is required for neural progenitor cell proliferation and survival. |
Zebrafish exoc7 knockout, exome sequencing in human families, EXOC7 splice variant modeling in vitro |
Genetics in medicine |
Medium |
32103185
|
| 2021 |
Exoc7 (Exo70) interacts with the E3 ubiquitin ligase Prpf19 and modulates levels of polyglutamine-expanded ataxin-3 (ATXN3-polyQ) in an opposite manner to Prpf19; Exoc7 exerts its effect by regulating the E3 ligase function of Prpf19 on ATXN3-polyQ ubiquitination and degradation. |
Co-IP, Exoc7 knockdown in mammalian and Drosophila models, polyQ protein level and toxicity assays, genetic epistasis |
Cell death & disease |
Medium |
33542212
|
| 2021 |
Exo70 contributes to cisplatin resistance in ovarian cancer cells by promoting exocytosis-mediated efflux of cisplatin. Cisplatin induces autophagy-lysosomal degradation of Exo70 via AMPK/mTOR phosphorylation modulation; stabilization of Exo70 under prolonged cisplatin treatment drives acquired resistance. |
Exo70 knockdown/overexpression, cisplatin efflux assay, autophagy-lysosome pathway analysis, in vitro and in vivo tumor models |
Cancers |
Medium |
34298686
|
| 2024 |
Exo70 is transamidated on Gln5 (with Lys56 of cystatin A) by transglutaminases TGM1 and TGM3; this modification enhances Exo70's assembly with other exocyst subunits, MMP secretion, invadopodia formation, and integrin delivery. Tumor suppressor LKB1 phosphorylates TGM1/TGM3 to inhibit their interaction with Exo70 and block this transamidation. |
Mass spectrometry for PTM identification, mutagenesis, Co-IP for complex assembly, in vitro transglutaminase assay, invasion assays, in vivo mouse model |
Cell reports |
High |
39146185
|
| 2022 |
The brain-specific Cdc42b isoform (but not ubiquitous Cdc42u) interacts with Exo70 in mammalian neurons. Inactivation of Arhgef7 or Cdc42b interferes with exocytosis of post-Golgi vesicles in the growth cone and with axon formation, placing Cdc42b upstream of Exo70-dependent exocytosis in neuronal polarity. |
Isoform-specific interaction assays, Arhgef7/Cdc42b conditional inactivation, live imaging of post-Golgi vesicle exocytosis in growth cones |
Life science alliance |
Medium |
36543541
|
| 2015 |
GIV/Girdin directly and constitutively binds the exocyst subunit Exo70 and associates with GLUT4-storage vesicles upon insulin stimulation. Without GIV or its GEF function, membrane association of Exo70 and insulin-stimulated exocytosis of GLUT4 vesicles are impaired. |
Pulldown, Co-IP, subcellular fractionation, GLUT4 exocytosis assay in adipocytes |
Biochemical and biophysical research communications |
Medium |
26514725
|
| 2021 |
Exo70 undergoes redistribution from the plasma membrane microsomal fraction to the synaptic compartment after traumatic brain injury; in the synaptic compartment, exocyst complex assembly and its interaction with GluN2B are increased, suggesting Exo70 modulates GluN2B synaptic availability after brain trauma. |
Subcellular fractionation, Co-IP of Exo70 with GluN2B, immunoblotting after repeated mild TBI model |
Biological research |
Medium |
33593425
|
| 2024 |
Exo70 promotes pancreatic cancer cell invasion and metastasis by regulating secretion of tumor exosomes; Exo70 knockdown or ES2 inhibitor treatment inhibits exosome secretion and increases accumulation of cellular vesicles. Exo70 also increases exosomal PD-L1 expression, contributing to immune escape. |
Exo70 knockdown, ES2 inhibitor treatment, nanoparticle tracking for exosome quantification, in vivo mouse metastasis model |
Cancers |
Medium |
38254825
|
| 2025 |
Cytoplasmic METTL3 interacts with EXOC7 and stabilizes it; METTL3 also regulates m6A-dependent alternative splicing of EXOC7 promoting expression of a more aggressive isoform. Silencing METTL3 (but not inhibiting its catalytic activity) impairs vesicle trafficking, the breast cancer secretome, and invadopodia formation. |
Co-IP, RIP, METTL3 knockdown vs. catalytic inhibition, vesicle trafficking assay, invasion assay |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.26.656168
|
| 2018 |
In Drosophila, Exo70 genetically interacts with ralA to regulate synaptic growth at the NMJ. Loss of Exo70 blocks JNK signaling-, activity-, and temperature-induced synaptic outgrowths and impairs integral membrane protein transport to the cell surface at synaptic terminals. |
Drosophila exo70 mutant alleles, genetic epistasis with ralA, electrophysiology, live imaging, surface protein trafficking assay |
The Journal of neuroscience |
High |
30209205
|