AtSEC22 Regulates Cell Morphogenesis via Affecting Cytoskeleton Organization and Stabilities

The plant cytoskeleton forms a stereoscopic network that regulates cell morphogenesis. The cytoskeleton also provides tracks for trafficking of vesicles to the target membrane. Fusion of vesicles with the target membrane is promoted by SNARE proteins, etc. The vesicle-SNARE, Sec22, regulates membrane trafficking between the ER and Golgi in yeast and mammals. Arabidopsis AtSEC22 might also regulate early secretion and is essential for gametophyte development. However, the role of AtSEC22 in plant development is unclear. To clarify the role of AtSEC22 in the regulation of plant development, we isolated an AtSEC22 knock-down mutant, atsec22-4, and found that cell morphogenesis and development were seriously disturbed. atsec22-4 exhibited shorter primary roots (PRs), dwarf plants, and partial abortion. More interestingly, the atsec22-4 mutant had less trichomes with altered morphology, irregular stomata, and pavement cells, suggesting that cell morphogenesis was perturbed. Further analyses revealed that in atsec22-4, vesicle trafficking was blocked, resulting in the trapping of proteins in the ER and collapse of structures of the ER and Golgi apparatus. Furthermore, AtSEC22 defects resulted in impaired organization and stability of the cytoskeleton in atsec22-4. Our findings revealed essential roles of AtSEC22 in membrane trafficking and cytoskeleton dynamics during plant development.

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Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement

International Journal of Molecular Sciences ◽

10.3390/ijms222111727 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11727

Author(s):

Maria J. Sarmento ◽

Luís Borges-Araújo ◽

Sandra N. Pinto ◽

Nuno Bernardes ◽

Joana C. Ricardo ◽

...

Keyword(s):

Plasma Membrane ◽

Hela Cells ◽

Membrane Trafficking ◽

Actin Polymerization ◽

Fluorescent Proteins ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Cellular Functions ◽

Cytoskeleton Organization

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential plasma membrane component involved in several cellular functions, including membrane trafficking and cytoskeleton organization. This function multiplicity is partially achieved through a dynamic spatiotemporal organization of PI(4,5)P2 within the membrane. Here, we use a Förster resonance energy transfer (FRET) approach to quantitatively assess the extent of PI(4,5)P2 confinement within the plasma membrane. This methodology relies on the rigorous evaluation of the dependence of absolute FRET efficiencies between pleckstrin homology domains (PHPLCδ) fused with fluorescent proteins and their average fluorescence intensity at the membrane. PI(4,5)P2 is found to be significantly compartmentalized at the plasma membrane of HeLa cells, and these clusters are not cholesterol-dependent, suggesting that membrane rafts are not involved in the formation of these nanodomains. On the other hand, upon inhibition of actin polymerization, compartmentalization of PI(4,5)P2 is almost entirely eliminated, showing that the cytoskeleton network is the critical component responsible for the formation of nanoscale PI(4,5)P2 domains in HeLa cells.

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The Role of Cell Adhesion and Cytoskeleton Dynamics in the Pathogenesis of the Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.649082 ◽

2021 ◽

Vol 9 ◽

Author(s):

Sabeeha Malek ◽

Darius V. Köster

Keyword(s):

Extracellular Matrix ◽

Cell Adhesion ◽

Genetic Basis ◽

Joint Hypermobility ◽

Cytoskeleton Organization ◽

Cellular Processes ◽

Membrane Bound ◽

Spectrum Disorders ◽

Cytoskeleton Dynamics

The Ehlers-Danlos syndromes (EDS) are a group of 13 disorders, clinically defined through features of joint hypermobility, skin hyperextensibility, and tissue fragility. Most subtypes are caused by mutations in genes affecting the structure or processing of the extracellular matrix (ECM) protein collagen. The Hypermobility Spectrum Disorders (HSDs) are clinically indistinguishable disorders, but are considered to lack a genetic basis. The pathogenesis of all these disorders, however, remains poorly understood. Genotype-phenotype correlations are limited, and findings of aberrant collagen fibrils are inconsistent and associate poorly with the subtype and severity of the disorder. The defective ECM, however, also has consequences for cellular processes. EDS/HSD fibroblasts exhibit a dysfunctional phenotype including impairments in cell adhesion and cytoskeleton organization, though the pathological significance of this has remained unclear. Recent advances in our understanding of fibroblast mechanobiology suggest these changes may actually reflect features of a pathomechanism we herein define. This review departs from the traditional view of EDS/HSD, where pathogenesis is mediated by the structurally defective ECM. Instead, we propose EDS/HSD may be a disorder of membrane-bound collagen, and consider how aberrations in cell adhesion and cytoskeleton dynamics could drive the abnormal properties of the connective tissue, and be responsible for the pathogenesis of EDS/HSD.

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MOLECULAR ASPECTS OF SARCOPENIA PATHOGENESIS IN CHRONOC KIDNEY DISEASE: INTEGRATED ROLE OF mTOR

Nephrology (Saint-Petersburg) ◽

10.24884/1561-6274-2018-22-5-9-16 ◽

2018 ◽

Vol 22 (5) ◽

pp. 9-16 ◽

Cited By ~ 3

Author(s):

M. Z. Gasanov

Keyword(s):

Kidney Disease ◽

Muscle Mass ◽

Protein Metabolism ◽

Mammalian Target Of Rapamycin ◽

Healthy Person ◽

Scientific Review ◽

Cytoskeleton Organization ◽

Molecular Aspects ◽

End Stage

In recent decades, the main pathogenetic mechanisms for maintaining muscle mass and strength have been discovered. Most of the scientific papers on the molecular aspects of the pathogenesis of sarcopenia were focused on the Akt-signaling pathway. The subject of the study were people of elderly and senile age, immobilized patients, patients with CKD 1-4 stages, animals. However, recently more attention has been paid to the role of protein – the mammalian target of rapamycin mTOR. It seems to be a key link in the control of muscle mass and is a promising marker in understanding the mechanisms of the pathogenesis of sarcopenia. Its importance in protein metabolism in patients with end stage kidney disease is not studied and requires further research. The presented scientific review contains information on the role of mTOR and its components – mTORC1 and mTORC2 in maintaining muscle mass and strength in a healthy person and in the formation of sarcopenia in patients with CKD. The general aid of mTORC1 complex is regulation of protein production which is necessary for cell growth and differentiation. mTORC2 complex functions are not enough studied. It is established that it plays important role in such biological processes as cytoskeleton organization, intracellular homeostasis maintaining, so it provides cell resistance and cell survivability in negative external and internal impulses. mTOR protein can be considered as promising molecular marker in diagnostics of protein metabolism early disturbances in patients with CKD and also as additory factor of sarcopenia severity assessment.

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Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22094425 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4425

Author(s):

Alazne Arrazola Arrazola Sastre ◽

Miriam Luque Luque Montoro ◽

Hadriano M. Lacerda ◽

Francisco Llavero ◽

José L. Zugaza

Keyword(s):

Membrane Trafficking ◽

Neurodegenerative Disorders ◽

Synaptic Vesicles ◽

Intracellular Trafficking ◽

Small Gtpases ◽

Constant Flow ◽

Parkinson’S Diseases ◽

The Central Nervous System ◽

Arf Gtpases

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration.

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Kindlin-2 mediates mechanotransduction in bone by regulating expression of Sclerostin in osteocytes

Communications Biology ◽

10.1038/s42003-021-01950-4 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Lei Qin ◽

Xuekun Fu ◽

Jing Ma ◽

Manxia Lin ◽

Peijun Zhang ◽

...

Keyword(s):

Bone Loss ◽

Mechanical Stimulation ◽

Fluid Shear Stress ◽

Weight Bearing ◽

Underlying Mechanism ◽

Long Bones ◽

Cell Orientation ◽

Cytoskeleton Organization

AbstractOsteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.

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