| 2006 |
Amot binds the Cdc42 RhoGAP Rich1 via its coiled-coil domain and is thereby targeted to a tight junction complex containing the PDZ-domain proteins Pals1, Patj, and Par-3 in MDCK epithelial cells. The coiled-coil domain of Amot is required for apical membrane localization and for relocalization of Pals1 and Par-3 to internal puncta. |
Functional and proteomic screens, co-immunoprecipitation, domain mutagenesis, confocal imaging in MDCK cells |
Cell |
High |
16678097
|
| 2008 |
Amot forms a ternary complex with the PDZ protein Patj (or Mupp1) and the RhoGEF Syx, and this complex controls spatial targeting of RhoA activity to lamellipodia in migrating endothelial cells. Amot interacts with Syx through its C-terminal PDZ-binding motif. |
Peptide pull-down, yeast two-hybrid screening, FRET analysis of RhoA activity, morpholino knockdown in zebrafish |
Blood |
High |
18824598
|
| 2010 |
Amot contains a novel lipid-binding domain (later termed ACCH domain) that selectively binds membranes containing monophosphorylated phosphatidylinositols and cholesterol with high affinity, enables membrane tubulation in vitro, and targets Amot to juxtanuclear endocytic recycling compartments marked by Rab11 and Arf6. |
Lipid-binding assays, in vitro membrane tubulation assay, fluorescence co-localization with Rab11/Arf6/cholesterol markers, cell fractionation |
The Journal of biological chemistry |
High |
20080965
|
| 2011 |
Amot80 (the 80 kDa isoform) promotes ERK1/2-dependent proliferation of mammary epithelial cells; a mutant lacking the polarity protein interaction domain fails to enhance ERK1/2-dependent proliferation, indicating this domain is required for the pro-proliferative effect. |
Isoform expression in MCF7 and MCF10A cells, Matrigel 3D culture, ERK1/2 activity assays, domain-deletion mutagenesis |
Cancer research |
Medium |
21285250
|
| 2015 |
AMOT interacts dynamically with the endosomal integral membrane protein endotubin (EDTB) at the endosomal membrane; EDTB competes with YAP for binding to AMOT in subconfluent cells. Overexpression of EDTB displaces YAP from AMOT, promoting YAP nuclear translocation and an overgrowth phenotype in a YAP-dependent manner. |
Co-immunoprecipitation, overexpression of full-length and cytoplasmic-domain EDTB, soft-agar growth assay, YAP nuclear translocation imaging |
Molecular biology of the cell |
Medium |
25995376
|
| 2017 |
Active Rho GTPase prevents phosphorylation of Amot Ser176, stabilizing the Amot–F-actin interaction and restricting Amot–Nf2 binding. Additionally, Rho directly binds the coiled-coil domain of Amot to attenuate Amot–Nf2 association, thereby suppressing Hippo signaling in trophectoderm cells of the blastocyst. |
Inhibitor/activator screen in blastocysts, co-immunoprecipitation, phosphorylation assays, domain mapping |
Development (Cambridge, England) |
Medium |
28947533
|
| 2017 |
CREB transcriptionally activates Mpp7, which in turn controls the subcellular localization and protein level of AMOT; MPP7 and AMOT are individually required for YAP1 nuclear accumulation and for the proliferative state of myoblasts. Thus AMOT functions downstream of CREB-MPP7 to relay signals to YAP1 in muscle satellite cells. |
Conditional knockout mice, loss-of-function in myoblasts, subcellular fractionation/immunofluorescence, Western blot |
Cell reports |
Medium |
29091764
|
| 2017 |
DUB3 deubiquitylating enzymes regulate the protein stability of AMOT family members (as well as LATS kinases and the E3 ligase ITCH), thereby modulating Hippo pathway activity and YAP/TAZ levels. |
Overexpression and knockdown of DUB3 in cell lines, Western blot for protein stability, ubiquitination assays |
PloS one |
Medium |
28061504
|
| 2019 |
Amot is required for dendritic morphogenesis in hippocampal neurons and Purkinje cells. Its function in dendrite growth depends on interaction with Yap1 and does not require TEAD transcription factors; instead, Amot and Yap1 regulate dendrite arborization by affecting phosphorylation of S6 kinase and its target S6 ribosomal protein. Conditional deletion of Amot in neurons reduces Purkinje cell dendritic tree complexity and impairs motor coordination. |
Conditional neuronal knockout mice, in vitro hippocampal culture knockdown, immunofluorescence, Western blot for S6K/S6 phosphorylation, motor behavior assays |
PLoS biology |
High |
31042703
|
| 2019 |
The lncRNA UCA1 directly binds AMOT protein (identified by in vivo RNA antisense purification), enhances the AMOT–YAP interaction, and promotes YAP dephosphorylation and nuclear translocation. Loss-of-function experiments confirm AMOT mediates YAP activation downstream of UCA1. |
In vivo RNA antisense purification (iRAP), RPPA, co-immunoprecipitation, loss-of-function siRNA, YAP phosphorylation and nuclear translocation assays |
iScience |
Medium |
31307004
|
| 2021 |
AMOT binds Talin and is an essential component of the endothelial integrin adhesome; endothelial-specific deletion of Amot in mice inhibits tip cell migration, filopodia extension, and vascular network expansion. Amot relays mechanical forces between fibronectin and the cytoskeleton. |
Endothelial-specific conditional knockout mice, in vitro molecular binding assays, traction force measurements, retinal and tumor vascular imaging |
Cell reports |
High |
34433061
|
| 2021 |
AMOT PPxY motifs interact with NEDD4L WW domains to promote HIV-1 virion envelopment and infectivity. The AMOT PPxY1–NEDD4L WW3 interaction has unusually high affinity due to complementary ionic and hydrophobic contacts beyond the WW-PPxY core, and is the dominant interaction driving HIV-1 release. Structural analysis revealed the molecular basis of this selectivity. |
Structural analysis (X-ray crystallography implied by 'comparative structural analyses'), binding affinity measurements, site-directed mutagenesis of PPxY motifs and WW domains, HIV-1 virological infectivity assays |
The Journal of biological chemistry |
High |
34284061
|
| 2021 |
Fragment-based X-ray crystallography resolved the first structure of the 14-3-3 binding motif of Amot-p130, characterizing the binding mode and affinities of the 14-3-3/Amot-p130 protein–protein interaction interface. |
X-ray crystallography, fragment-based screening, binding affinity measurements (SPR/ITC implied) |
Current research in structural biology |
Medium |
35036934
|
| 2022 |
RICH1 competes with Merlin for binding to Amot-p80 via its BAR domain; this competition displaces Amot-p80 from the Amot-Merlin complex and activates the Hippo kinase cascade, suppressing YAP/TAZ and breast cancer stem cell traits. Deletion of the BAR domain of RICH1 abolishes its ability to displace Merlin from Amot-p80. |
Co-immunoprecipitation, domain deletion mutagenesis (BAR domain), loss-of-function in MCF10A cells, stem cell trait assays |
Cell death & disease |
Medium |
35064101
|
| 2023 |
WWC1 and WWC2 directly bind AMOT family proteins (Motins) and recruit the deubiquitylase USP9X to deubiquitinate and stabilize Motins. Neuron-specific deletion of Wwc1/2 in mice reduces Motin protein levels, decreases dendritic spine density in cortex and hippocampus, and impairs memory/learning; ectopic AMOT expression partially rescues these neuronal phenotypes. |
Direct binding assays, USP9X recruitment and deubiquitination assays, conditional double-knockout mice, immunofluorescence of dendritic spines, cognitive behavioral tests, rescue by AMOT overexpression |
Cell death & disease |
High |
37528078
|
| 2024 |
AMOT nuclear translocation (driven by actomyosin activity consequent to cell size reduction) suppresses YAP activity and promotes definitive endoderm differentiation of human pluripotent stem cells. Blocking actomyosin activity prevents both AMOT nuclear translocation and endoderm specification. |
Hypertonic pressure treatment, chemical inhibitors of actomyosin, immunofluorescence of AMOT and YAP subcellular localization, endoderm marker expression assays |
Stem cell reports |
Medium |
39094563
|
| 2024 |
AMOT expression gradually decreases during epiblast formation through tankyrase-mediated degradation; SOX2 expression in the ICM is necessary for this reduction of AMOT and consequent decrease in YAP phosphorylation, enabling YAP nuclear localization. Blastocoel expansion and AMOT degradation act in parallel to promote YAP nuclear translocation. |
Mouse preimplantation embryo analysis, tankyrase inhibition, SOX2 loss-of-function, immunofluorescence of AMOT/YAP phosphorylation and localization |
Developmental biology |
Medium |
39486633
|
| 2025 |
AMOT protein stability serves as the primary mechanical rheostat controlling YAP/TAZ: AMOT is stable in mechanically inhibited cells where it sequesters YAP/TAZ in the cytoplasm, but in mechanically activated cells, microtubules reorganize into a radial centrosomal array, allowing dynein/dynactin-mediated retrograde transport of AMOT to the pericentrosomal proteasome for rapid degradation. LATS kinases phosphorylate AMOT and shield it from this degradation route, thereby indirectly restraining YAP/TAZ. Loss of AMOT renders cells insensitive to mechanical modulations. |
Live-cell imaging, AMOT degradation assays, dynein/dynactin co-immunoprecipitation, NLP1 overexpression to restore centrosomal condensation, AMOT knockout cells, LATS phosphorylation assays, proteasome inhibition |
Nature cell biology |
High |
41034521
|
| 2025 |
A pathogenic N-terminal truncation of AMOT (loss of first 91 amino acids) causes loss of both an N-degron degradation signal and the tankyrase-binding domain, leading to abnormally increased AMOT protein levels that disrupt cellular barrier integrity and cause X-linked congenital hydrocephalus in affected males. |
Exome sequencing, expression of truncation mutant, protein stability assays, barrier integrity assays in cells |
The Journal of clinical investigation |
Medium |
40892511
|
| 2025 |
SIPA1L3 interacts with AMOT through its PDZ domain, inhibiting the binding of AMOT to Patj (PALS1-associated tight junction protein) and decreasing AMOT anchoring to tight junctions, thereby promoting a malignant phenotype in NSCLC. |
Co-immunoprecipitation, PDZ domain mutant of SIPA1L3, Western blot, immunofluorescence, in vitro and in vivo proliferation/invasion assays |
Medicine |
Medium |
41088697
|