Myosin 1c: A novel regulator of glucose uptake in brown adipocytes

Åslund, Alice; Bokhari, Muhammad Hamza; Wetterdal, Erika; Martin, René; Knölker, Hans‐Joachim; Bengtsson, Tore

doi:10.1016/j.molmet.2021.101247

Cited by 4 publications

(2 citation statements)

References 66 publications

(90 reference statements)

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“…Finally, MYO1C (OMIM*606538), which is downregulated in male and female cohorts with MDS, is a myosin involved in cytoskeletal organisation and vesicle trafficking and when depleted, induces fragmentation of the Golgi complex, the loss of cellular F‐actin and a delay in transport (Capmany et al, 2019). MYO1C is also involved in the recycling of glucose transporters in response to insulin (Åslund et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Multi‐omics in MECP2 duplication syndrome patients and carriers

Pascual‐Alonso,

Xiol,

Smirnov

et al. 2024

Eur J of Neuroscience

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MECP2 duplication syndrome (MDS) is an X‐linked neurodevelopmental disorder caused by the gain of dose of at least the genes MECP2 and IRAK1 and is characterised by intellectual disability (ID), developmental delay, hypotonia, epilepsy and recurrent infections. It mainly affects males, and females can be affected or asymptomatic carriers. Rett syndrome (RTT) is mainly triggered by loss of function mutations in MECP2 and is a well described syndrome that presents ID, epilepsy, lack of purposeful hand use and impaired speech, among others. As a result of implementing omics technology, altered biological pathways in human RTT samples have been reported, but such molecular characterisation has not been performed in patients with MDS. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 patients with RTT, and performed multi‐omics (RNAseq and proteomics) analysis. Here, we provide a thorough description and compare the shared and specific dysregulated biological processes between the cohorts. We also highlight the genes TMOD2, SRGAP1, COPS2, CNPY2, IGF2BP1, MOB2, VASP, FZD7, ECSIT and KIF3B as biomarker and therapeutic target candidates due to their implication in neuronal functions. Defining the RNA and protein profiles has shown that our four cohorts are less alike than expected by their shared phenotypes.

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Section: Discussionmentioning

confidence: 99%

Multi‐omics in MECP2 duplication syndrome patients and carriers

Pascual‐Alonso,

Xiol,

Smirnov

et al. 2024

Eur J of Neuroscience

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show abstract

“…STK17B is upregulated in MDS males but downregulated in females. Finally, MYO1C (OMIM*606538), which is downregulated in male and female MDS cohorts, is a myosin involved in cytoskeletal organisation and vesicle trafficking and when depleted, induces fragmentation of the Golgi complex, the loss of cellular F-actin and a delay in transport 42 .MYO1C is also involved in the recycling of glucose transporters in response to insulin 43 . MDS male and female cohorts share some biological pathways, such as cellular adhesion, vesicular activity and synapses; which are downregulated.…”

Section: Comparison Between Female and Male Mds Patientsmentioning

confidence: 99%

Multi-omics in MECP2 duplication syndrome patients and carriers.

Pascual-Alonso,

Xiol,

Smirnov

et al. 2024

Preprint

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MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by the gain of dose of at least the genes MECP2 and IRAK1 and is characterised by intellectual disability (ID), developmental delay, hypotonia, epilepsy and recurrent infections. It mainly affects males, and females can be affected or asymptomatic carriers. Rett syndrome (RTT) is mainly triggered by loss of function mutations in MECP2 and is a well described syndrome that presents ID, epilepsy, lack of purposeful hand use and impaired speech, among others. As a result of implementing omics technology, altered biological pathways in human RTT samples have been reported, but such molecular characterisation has not been performed in MDS patients. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 RTT patients, and performed multi-omics (RNAseq and proteomics) analysis. Here, we provide a thorough description and compare the shared and specific dysregulated biological processes between the cohorts. We also highlight the genes TMOD2, SRGAP1, COPS2, CNPY2, IGF2BP1, MOB2, VASP, FZD7, ECSIT andKIF3B as biomarker and therapeutic target candidates due to their implication in neuronal functions. Defining the RNA and protein profiles has shown that our four cohorts are less alike than expected by their shared phenotypes.

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An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells

Kyriazi,

Voth,

Bader

et al. 2024

Nat Commun

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Aberrant Ras homologous (Rho) GTPase signalling is a major driver of cancer metastasis, and GTPase-activating proteins (GAPs), the negative regulators of RhoGTPases, are considered promising targets for suppressing metastasis, yet drug discovery efforts have remained elusive. Here, we report the identification and characterization of adhibin, a synthetic allosteric inhibitor of RhoGAP class-IX myosins that abrogates ATPase and motor function, suppressing RhoGTPase-mediated modes of cancer cell metastasis. In human and murine adenocarcinoma and melanoma cell models, including three-dimensional spheroid cultures, we reveal anti-migratory and anti-adhesive properties of adhibin that originate from local disturbances in RhoA/ROCK-regulated signalling, affecting actin-dynamics and actomyosin-based cell-contractility. Adhibin blocks membrane protrusion formation, disturbs remodelling of cell-matrix adhesions, affects contractile ring formation, and disrupts epithelial junction stability; processes severely impairing single/collective cell migration and cytokinesis. Combined with the non-toxic, non-pathological signatures of adhibin validated in organoids, mouse and Drosophila models, this mechanism of action provides the basis for developing anti-metastatic cancer therapies.

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Myosin 1c: A novel regulator of glucose uptake in brown adipocytes

Cited by 4 publications

References 66 publications

Multi‐omics in MECP2 duplication syndrome patients and carriers

Multi‐omics in MECP2 duplication syndrome patients and carriers

Multi-omics in MECP2 duplication syndrome patients and carriers.

An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells

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