| 2010 |
Myo9b is a RhoGAP expressed in immune cells that spatially coordinates Rho activity to enable macrophage spreading, polarization, and lamellipodia formation. Myo9b-deficient macrophages fail to generate lamellipodia in response to chemoattractant and show severely impaired migration; pharmacological inhibition of Rho rescues the spreading/polarization defect, placing Myo9b upstream of RhoA in the motility pathway. |
Myo9b knockout mice; macrophage spreading/migration assays; Rho inhibitor rescue (epistasis); in vivo peritoneal recruitment assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
20566876
|
| 2015 |
Myo9b is a ROBO-interacting protein that suppresses RhoA activity via its RhoGAP domain. The ROBO intracellular domain directly binds the Myo9b RhoGAP domain and inhibits its GAP activity, so SLIT-dependent ROBO activation leads to increased RhoA-GTP by relieving Myo9b-mediated RhoA suppression. Structural analysis identified a unique patch in the Myo9b RhoGAP domain that specifically recognizes RhoA. |
Co-immunoprecipitation (ROBO–Myo9b interaction); in vitro GAP inhibition assay; structural analysis of RhoGAP domain; RhoA-GTP pull-down; cell migration assays; murine tumor/metastasis model |
The Journal of clinical investigation |
High |
26529257
|
| 2016 |
Myo9b-RhoGAP accelerates RhoA GTP hydrolysis by a dual-arginine-finger mechanism: the first arginine finger inserts into the nucleotide-binding pocket of RhoA (canonical), while a second arginine finger anchors the Switch I loop of RhoA and stabilizes the transition state, compensating for the absence of the auxiliary asparagine found in canonical RhoGAP domains. Mutagenesis of either arginine finger impairs catalytic activity and cell migration. |
Crystal structure of Myo9b-RhoGAP in complex with GDP-bound RhoA and magnesium fluoride; active-site mutagenesis; in vitro GAP activity assay; cell migration assay |
Journal of molecular biology |
High |
27363609
|
| 2017 |
The transcription factor KLF5 directly binds the Myo9b promoter and activates Myo9b transcription. In macrophages, KLF5-driven Myo9b expression is required for podosome formation (Myo9b colocalizes with F-actin, cortactin, vinculin, and Tks5 at podosomes) and migration. KLF5 knockdown increases RhoA-GTP, placing Myo9b downstream of KLF5 and upstream of RhoA inhibition. |
Luciferase reporter assay (KLF5 binding to Myo9b promoter); myeloid-specific KLF5 KO mice; gain/loss-of-function experiments; co-immunostaining; RhoA-GTP pull-down; macrophage migration and time-lapse imaging |
Circulation research |
High |
28115390
|
| 2020 |
PKA and PKG phosphorylate Myo9b at serine 1354 in human platelets. This phosphorylation enhances Myo9b's GAP activity, leading to reduced RhoA-GTP levels. This mechanism mediates cyclic nucleotide-dependent inhibition of RhoA in platelets, as RhoA itself is not directly phosphorylated by PKA under these conditions. |
Phosphoproteomics of human platelets; Western blotting and Phos-tag gel electrophoresis; pull-down assays for GAP activity; transfected HEK293T cells as validation |
Journal of thrombosis and haemostasis : JTH |
High |
32692911
|
| 2020 |
Myo9b accumulates in lamellipodial extensions as a function of its motor activity (motor mutants fail to accumulate). Local, not global, GAP activity of Myo9b is required to rescue cell morphology and directional migration in Myo9b-deficient macrophage-like cells. Rac-induced actin polymerization recruits Myo9b, which then locally inhibits Rho at the leading edge. |
Myo9b-deficient HL-60-derived macrophages reconstituted with motor-dead and GAP-dead Myo9b mutants; live-cell imaging; cell migration assays; fluorescent Myo9b localization |
The Journal of biological chemistry |
High |
33268376
|
| 2012 |
Myo9b is a critical RhoA GAP in cortical neurons: knockdown of Myo9b in cultured cortical neurons or developing cortex reduces dendrite length and number, and inhibition of RhoA/ROCK signaling rescues the dendritic morphology defects caused by Myo9b knockdown, placing Myo9b upstream of RhoA/ROCK in dendritic development. |
RNA interference knockdown in rat cortical neurons and in vivo cortex; dendritic morphology quantification; RhoA/ROCK inhibitor rescue epistasis |
Cerebral cortex |
Medium |
22250289
|
| 2017 |
Myo9b knockout impairs bone growth in mice. In osteoblastic cells, Myo9b is distributed in stress fibers and focal adhesions; its loss causes poor cell spreading and detachment, and reduces IGF-1-induced spreading and chemotaxis (but not responses to PDGF or BMP-2). Loss of Myo9b redistributes activated IGF-1 receptor from stress fibers and focal adhesions into nuclei, suggesting Myo9b regulates IGF1R subcellular localization and accessibility. |
Myo9b KO mice (micro-CT, histomorphometry); primary osteogenic cell culture; RNAi knockdown of Myo9b in MC3T3-E1 cells; IGF-1 chemotaxis and spreading assays; immunofluorescence of IGF1R localization |
Journal of bone and mineral research |
Medium |
28585695
|
| 2022 |
Myo9b is required for ocular lens vesicle morphogenesis. Myo9b-deficient mice show microphthalmia and cataracts; embryonic lens placode invagination is shallow and conical rather than spherical, with mislocalized F-actin and adherens junctions, indicating Myo9b coordinates mechanical forces between epithelial cells during lens pit formation. |
Myo9b KO mouse embryo analysis; immunostaining of F-actin and adherens junctions; Pax6 expression control |
Developmental dynamics |
Medium |
36008362
|
| 2022 |
Rare recessive variants in MYO9B cause Charcot-Marie-Tooth disease type 2 (CMT2) and isolated optic atrophy. A variant in the MYO9B motor domain impairs protein expression level and motor activity. Myo9b-null mice have degenerating axons in sciatic nerves and optic nerves, indicating Myo9b motor function is essential for axon maintenance in both peripheral and central nervous system. |
Whole-exome sequencing and targeted NGS in CMT2 families; functional studies of motor domain variant (protein expression, motor activity assay); Myo9b-null mouse nerve histopathology |
European journal of neurology |
Medium |
36260368
|
| 2023 |
Myo9b regulates dendritic cell (DC) migration and T-cell priming. A 33-bp deletion in the Myo9b motor domain (in ALR mice) impairs DC phenotypic and functional maturation and prevents autoimmune diabetes progression in NOD mice. A human MYO9B R133Q polymorphism enhances DC function. Knock-in of the ALR Myo9b allele into NOD mice recapitulates impaired DC migration and T-cell priming. |
Genomic comparative analysis; Myo9b knock-in mouse models; DC migration and T-cell priming assays in vitro and in vivo; spontaneous diabetes incidence monitoring |
Nature communications |
High |
37749140
|
| 2024 |
MIRO2 binds MYO9B and cooperates with it to promote cancer cell invasion. Knockdown of MIRO2's binding partner MYO9B reduces tumor cell invasion and phenocopies MIRO2 depletion, resulting in increased active RhoA. Dual ablation of MIRO2 and RhoA fully rescues tumor cell invasion, and MIRO2 requires MYO9B to drive invasion, defining a MIRO2–MYO9B–RhoA axis in metastasis. |
Co-immunoprecipitation (MIRO2–MYO9B interaction); RNAi knockdown of MYO9B; RhoA-GTP measurement; dual MIRO2/RhoA knockdown epistasis; in vitro invasion assays; mouse metastasis models |
Cell reports |
Medium |
39723893
|
| 2025 |
Myo9b deficiency in head and neck squamous cell carcinoma (HNSC) cells upregulates HIF1α signaling, which in turn upregulates c-Myc, inducing stem-like phenotypes; c-Myc then upregulates STAT2 signaling, contributing to cisplatin resistance. |
Western blotting and immunostaining; CCK8 proliferation and Transwell migration assays; 3D Matrigel primary tumor cell culture; STAT2 inhibitor treatment |
Biochimica et biophysica acta. General subjects |
Low |
40518028
|
| 2025 |
RhoA GAP Myo9b regulates β2-integrin activation in neutrophils by controlling RhoA activity, which is required for chemokine- and selectin-induced talin-1 recruitment to β2-integrins. Myo9b deficiency causes RhoA overactivation, increases actin rearrangement, decreases neutrophil adhesion, crawling, and transmigration, and impairs neutrophil recruitment into the kidney during acute kidney injury. |
Myo9b KO mice; intravital microscopy (rolling, adhesion, crawling, transmigration); acute kidney injury models; talin-1 recruitment assays; RhoA-GTP measurement |
Blood |
High |
40504998
|
| 2025 |
CDK4 phosphorylates Myo9b at serine 1935 (S1935), and this phosphorylation activates Myo9b's RhoGAP function, thereby suppressing RhoA signaling and restricting TNBC cell migration. Loss or inhibition of CDK4 decreases Myo9b S1935 phosphorylation, enhances RhoA signaling, reorganizes actin networks, and increases cell migration. |
CRISPR/Cas9 CDK4 KO; CDK4/6 pharmacological inhibitor; phosphorylation site identification (S1935); RhoA activity assay; actin cytoskeleton imaging; migration assays in MDA-MB-231 cells |
bioRxivpreprint |
Medium |
|
| 2020 |
Myo9b deficiency in cancer cells (lung) suppresses malignant pleural effusion development by inhibiting migration. In immune cells, Myo9b deficiency decreases TH1 cell differentiation and increases TH17 cell differentiation via a TSAd-dependent pathway: Myo9b loss enriches the H3K27me3 repressive mark at the TSAd promoter, reducing TSAd expression, which shifts naive T cell fate toward TH17. |
Myo9b-deficient mouse model; in vitro T-cell differentiation assays; mRNA sequencing; ChIP for H3K27me3; siRNA knockdown of TSAd; in vivo MPE model |
Journal of immunology |
Medium |
33046503
|