| 2003 |
EHBP1 interacts with EHD2 via NPF repeats in EHBP1 binding to the C-terminal EH domain of EHD2. EHBP1 contains a calponin homology (CH) domain that links clathrin-mediated endocytosis to the actin cytoskeleton. siRNA-mediated knockdown of EHBP1 inhibits transferrin endocytosis into EEA1-positive endosomes and GLUT4 endocytosis in adipocytes. Overexpression of EHBP1 mediates extensive actin reorganization. |
siRNA knockdown, co-immunoprecipitation, domain interaction mapping, cell-based endocytosis assays, actin reorganization imaging |
The Journal of biological chemistry |
High |
14676205
|
| 2004 |
EHD1 interacts with EHBP1 through its EH domain, and both EHD1 and EHBP1 are required for perinuclear localization of GLUT4 and insulin-stimulated GLUT4 recycling in adipocytes. siRNA depletion of EHBP1 disrupts insulin-regulated GLUT4 movements and hexose transport. In contrast, EHD2 is not required for GLUT4 localization or translocation. |
siRNA knockdown, dominant-negative constructs, co-immunoprecipitation, immunofluorescence co-localization, glucose transport assay |
The Journal of biological chemistry |
High |
15247266
|
| 2010 |
C. elegans EHBP-1 was identified as a direct binding partner of RAB-10 via yeast two-hybrid. EHBP-1-GFP co-localizes with RFP-RAB-10 on endosomal structures in intestinal and neuronal cells. Loss-of-function of ehbp-1 phenocopies rab-10 mutants in endosome morphology and cargo localization defects, including disrupted transport of membrane proteins to the plasma membrane. RAB-8 and RAB-10 show redundancy in non-polarized cells where EHBP-1 also functions. |
Yeast two-hybrid, in vivo co-localization (GFP/RFP), genetic loss-of-function mutants, cargo localization assays in C. elegans |
Molecular biology of the cell |
High |
20573983
|
| 2016 |
In hepatocytes undergoing autophagy, Rab10 activity increases and Rab10 recruits EHBP1 and EHD2 to nascent autophagic membranes at the lipid droplet (LD) surface. Rab10 activation is essential for LC3 recruitment to the autophagosome and increases the association of EHBP1 and EHD2 with these membranes. Knockdown of Rab10 by siRNA or expression of a GTPase-defective Rab10 variant leads to LD accumulation, and EHBP1 and EHD2 together drive the engulfment of LDs during lipophagy. |
siRNA knockdown, GTPase-defective mutant expression, co-immunoprecipitation, fluorescence imaging, autophagy/lipophagy assays in hepatocytes |
Science advances |
High |
28028537
|
| 2013 |
Drosophila EHBP1 (dEHBP1) regulates the exocytosis of Scabrous (a positive regulator of Notch signaling), and its loss leads to supernumerary R8 photoreceptors due to defective lateral inhibition. dEHBP1 thus controls Notch signaling by trafficking distinct components (Scabrous vs. Delta) in different developmental contexts. |
Drosophila genetics (loss-of-function), cell fate analysis, epistasis with Notch pathway components, trafficking assays for Scabrous secretion |
Journal of cell science |
Medium |
23788431
|
| 2014 |
EHBP1 interacts with P-Rex1 (a guanine nucleotide exchange factor implicated in invasive growth) in PTEN-expressing prostate cancer cells, and EHBP1 is essential for the anti-invasive effect of atorvastatin. EHBP1 is involved in P2X7 signaling. Notably, the EHBP1-P-Rex1 interaction was not induced by extracellular ATP (the endogenous P2X7 ligand). |
Co-immunoprecipitation, siRNA knockdown, invasion assays, pharmacological inhibition |
Carcinogenesis |
Medium |
24451147
|
| 2020 |
The molecular mechanism of EHBP1 actin-binding activation was established: (1) EHBP1's N-terminal C2 domain associates with PI(3)P, PI(5)P, and phosphatidylserine, providing membrane targeting. (2) In the absence of Rab8 family members, the C-terminal bivalent Mical/EHBP Rab binding (bMERB) domain forms an intramolecular complex with the central calponin homology (CH) domain, auto-inhibiting actin binding. (3) Binding of active Rab8 to the bMERB domain relieves this autoinhibition, freeing the CH domain to interact with actin and drive membrane tubulation. Crystal/biochemical structures of the autoinhibited CH:bMERB complex and the active bMERB:Rab8 complex were determined and validated by structure-based mutagenesis. |
X-ray crystallography, in vitro biochemical binding assays, structure-based mutagenesis, actin binding assays, membrane tubulation assays, lipid binding assays |
Nature communications |
High |
32826901
|
| 2024 |
In Drosophila wing disc epithelium, Ehbp1 acts as a directional switch for polarized Wg/Wnt transport: AP-1 delivers Wg/Wnt basolaterally, and Ehbp1 competes with Wntless for AP-1 binding, thereby sequestering AP-1 and redirecting Wg/Wnt for apical delivery. Removing Ehbp1 coiled-coil motifs within its bMERB domain, or reducing Ehbp1 expression, leads to basolateral Wg/Wnt accumulation. This regulation of polarized Wnt delivery is conserved in vertebrates. |
Genetic epistasis (Drosophila), co-immunoprecipitation (AP-1 interaction), domain deletion mutants, cargo localization assays, vertebrate conservation experiments |
EMBO reports |
Medium |
39402333
|
| 2024 |
EHBP1 is critically involved in dendritic arbor formation in rat hippocampal neurons. A newly identified motif specific to chordate EHBP1 proteins mediates interaction with syndapin I (an F-BAR domain protein). This function does not require the Rab GTPase-binding domain but is strictly dependent on the syndapin I binding interface and syndapin I presence. EHBP1 forms ternary complexes with syndapin I and the actin nucleator Cobl at nascent dendritic branch sites. The C2 and CH domains of EHBP1 are also required for dendritic arborization. |
Gain-of-function and loss-of-function in primary rat hippocampal neurons, co-immunoprecipitation, domain deletion mutants, rescue experiments, live imaging of protein dynamics at dendritic branch sites |
The Journal of neuroscience |
High |
38129132
|
| 2025 |
EHBP1 promotes sortilin-mediated PCSK9 secretion, leading to LDL receptor (LDLR) degradation, decreased LDL uptake, and reduced TAZ (a fibrogenic effector) in the liver. EHBP1 deficiency disrupts the intracellular localization of retromer (a complex required for sortilin stabilization), thereby increasing hepatic cholesterol accumulation and MASH fibrosis. TNF-α/PPARα pathway suppresses EHBP1 in MASH. |
Loss-of-function and gain-of-function mouse models, mechanistic cell biology (retromer localization, PCSK9 secretion assays, LDLR degradation assays), immunofluorescence |
Cell metabolism |
High |
40015280
|
| 2025 |
In C. elegans, EHBP-1 localizes to recycling endosomes and captures RAB-10-positive lipoprotein exocytic carriers through its interaction with active RAB-10, promoting delivery of exocytic cargo to recycling endosomes. The mechanism requires synergy between EHBP-1's RAB-10-binding coiled-coil domain and its PI(4,5)P2-binding C2 domain. LST-6/DENND5 was identified as the GEF for RAB-10 in this post-Golgi pathway. After EHBP-1 capture, the exocyst complex carries out subsequent trafficking steps. |
C. elegans and mammalian cell genetics, live imaging, domain deletion mutants, GEF identification, epistasis with exocyst complex |
The Journal of cell biology |
Medium |
39982707
|
| 2026 |
EHBP1 localizes to the basal body and ciliary compartment of the primary cilium in human fibroblasts and RPE cells, and to the outer membrane of developing photoreceptors in retinal organoids. Dysfunction of INPP5E (due to patient mutations or CRISPR/Cas9 knockout) alters EHBP1 localization, placing EHBP1 in a ciliary functional module downstream of or regulated by INPP5E. |
Proximity-labeling proteomics (BioID), immunofluorescence localization in human fibroblasts/RPE, CRISPR/Cas9 knockout, patient-derived fibroblast analysis, retinal organoids |
Journal of cell science |
Medium |
41805112
|