Lef1 regulates caveolin expression and caveolin dependent endocytosis, a process necessary for Wnt5a/Ror2 signaling during Xenopus gastrulation

Puzik, Katharina; Tonnier, Veronika; Opper, Isabell; Eckert, Antonia Franziska; Zhou, Lu; Kratzer, Marie-Claire; Noble, Ferdinand le; Nienhaus, G. Ulrich; Gradl, Dietmar

doi:10.1038/s41598-019-52218-1

Cited by 9 publications

(9 citation statements)

References 51 publications

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“…The embryos displayed a minor shortening of the anterior–posterior axis (Fig. 1 B), which is likely caused by convergent extension defects as recently shown by Putzig et al 37 . However, as we did not target the injections to the mesoderm, we only observed mild morphological abnormalities.…”

Section: Resultssupporting

confidence: 75%

Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development

Breuer

Berger

Borchers

2020

Sci Rep

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Caveolins are essential structural proteins driving the formation of caveolae, specialized invaginations of the plasma membrane. Loss of Caveolin-1 (Cav1) function in mice causes distinct neurological phenotypes leading to impaired motor control, however, the underlying developmental mechanisms are largely unknown. In this study we find that loss-of-function of Xenopus Cav1 results in a striking swimming defect characterized by paralysis of the morphants. High-resolution imaging of muscle cells revealed aberrant sarcomeric structures with disorganized actin fibers. As cav1 is expressed in motor neurons, but not in muscle cells, the muscular abnormalities are likely a consequence of neuronal defects. Indeed, targeting cav1 Morpholino oligonucleotides to neural tissue, but not muscle tissue, disrupts axonal outgrowth of motor neurons and causes swimming defects. Furthermore, inhibition of voltage-gated sodium channels mimicked the Cav1 loss-of-function phenotype. In addition, analyzing axonal morphology we detect that Cav1 loss-of-function causes excessive filopodia and lamellipodia formation. Using rescue experiments, we show that the Cav1 Y14 phosphorylation site is essential and identify a role of RhoA, Rac1, and Cdc42 signaling in this process. Taken together, these results suggest a previously unrecognized function of Cav1 in muscle development by supporting axonal outgrowth of motor neurons.

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Section: Resultssupporting

confidence: 75%

Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development

Breuer

Berger

Borchers

2020

Sci Rep

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“…Lymphoid enhancer-binding factor 1 (LEF1) is a transcription factor involved in many diseases [3][4][5][6] . It belongs to the high-mobility group family that regulates gene expression by inducing structural alteration in the DNA helix 7 .…”

Section: Introductionmentioning

confidence: 99%

LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway

Wang¹,

Hao²,

Liu³

et al. 2020

Cell Death Dis

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Osteoarthritis (OA) is a joint disease that causes great pain to patients and imposes a tremendous burden on the world's medical resources. Regulatory noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), play an important role in OA progression. Here, we identified differential expression of transcription factor LEF1 that increased circRNA circRNF121 levels in normal and OA cartilage tissues. The expression of LEF1 and circRNF121 was positively associated with Mankin's scores. Alteration of circRNF121 mediated the degradation of extracellular mechanisms (ECM), apoptosis, and proliferation of chondrocytes. MiR-665 was identified as a direct regulatory target of circRNF121 and MYD88. Functional analysis showed that circRNF121 and MYD88 modulated ECM degradation, apoptosis, and proliferation of chondrocytes, which could be reversed by miR-665. MYD88 regulated the activity of the NF-кB signaling pathway by circRNF121 via sponging miR-665. Collectively, these data indicated that LEF1 impacted OA progression by modulating the circRNF121/miR-665/MYD88 axis via NF-кB pathway. Our research proposed a new molecular mechanism for the development of OA, and provided a prospective therapeutic target for OA.

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“…Another challenge is the intracellular barrier, affecting mainly the cellular uptake, which is a process of interaction between extracellular materials and cell membrane. There are various pathways involved in cellular uptake, including macropinocytosis [ 67 , 68 ], clathrin-dependent endocytosis [ 69 , 70 , 71 , 72 ], caveolin-dependent endocytosis [ 73 , 74 ], and other clathrin/caveolin-independent endocytoses [ 75 ]. Once vesicles are endocytosed by the cells, they will be trapped by the endosome ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy

Zhang

et al. 2022

Molecules

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Lipid-based nanoparticles (LBNPs) are biocompatible and biodegradable vesicles that are considered to be one of the most efficient drug delivery platforms. Due to the prominent advantages, such as long circulation time, slow drug release, reduced toxicity, high transfection efficiency, and endosomal escape capacity, such synthetic nanoparticles have been widely used for carrying genetic therapeutics, particularly nucleic acids that can be applied in the treatment for various diseases, including congenital diseases, cancers, virus infections, and chronic inflammations. Despite great merits and multiple successful applications, many extracellular and intracellular barriers remain and greatly impair delivery efficacy and therapeutic outcomes. As such, the current state of knowledge and pitfalls regarding the gene delivery and construction of LBNPs will be initially summarized. In order to develop a new generation of LBNPs for improved delivery profiles and therapeutic effects, the modification strategies of LBNPs will be reviewed. On the basis of these developed modifications, the performance of LBNPs as therapeutic nanoplatforms have been greatly improved and extensively applied in immunotherapies, including infectious diseases and cancers. However, the therapeutic applications of LBNPs systems are still limited due to the undesirable endosomal escape, potential aggregation, and the inefficient encapsulation of therapeutics. Herein, we will review and discuss recent advances and remaining challenges in the development of LBNPs for nucleic acid-based immunotherapy.

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Lef1 regulates caveolin expression and caveolin dependent endocytosis, a process necessary for Wnt5a/Ror2 signaling during Xenopus gastrulation

Cited by 9 publications

References 51 publications

Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development

Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development

LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway

Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy

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