Search results for: Cortactin
#33622779 
2021/02/22
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Abl2:cortactin interactions regulate dendritic spine stability via control of a stable filamentous actin pool.
Dendritic spines act as the receptive contacts at most excitatory synapses. Spines are enriched in a network of actin filaments comprised of two kinetically distinct pools. The majority of spine actin is highly dynamic and regulates spine size, structural plasticity, and postsynaptic density organization. The remainder of the spine actin network is more stable, but the function of this minor actin population is not well understood, as tools to study it have not been available. Previous work has shown that disruption of the Abl2/Arg nonreceptor tyrosine kinase in mice compromises spine stability and size. Here, using cultured hippocampal neurons pooled from both sexes of mice, we provide evidence that binding to cortactin tethers Abl2 in spines, where Abl2 and cortactin maintain the small pool of stable actin required for dendritic spine stability. Using fluorescence recovery after photobleaching of GFP-actin, we find that disruption of Abl2:cortactin interactions eliminates stable actin filaments in dendritic spines, significantly reducing spine density. A subset of spines remaining after Abl2 depletion retain their stable actin pool and undergo activity-dependent spine enlargement, associated with increased cortactin and GluN2B levels. Finally, tonic increases in synaptic activity rescue spine loss upon Abl2 depletion by promoting cortactin enrichment in vulnerable spines. Together, our findings strongly suggest Abl2:cortactin interactions promote spine stability by maintaining pools of stable actin filaments in spines.Dendritic spines contain two kinetically distinct pools of actin. The more abundant, highly dynamic pool regulates spine shape, size, and plasticity. The function of the smaller, stable actin network is not well understood, as tools to study it have not been available. We demonstrate here that Abl2 and its substrate and interaction partner, cortactin, are essential to maintain the stable pool in spines. Depletion of the stable actin pool via disruption of Abl2 or cortactin, or interactions between the proteins, significantly reduces spine stability. We also provide evidence that tonic increases in synaptic activity promote spine stability via enrichment of cortactin in spines, suggesting synaptic activity acts on the stable actin pool to stabilize dendritic spines.Juliana E Shaw, Michaela B C Kilander, Yu-Chih Lin, Anthony J Koleske
2602 related Products with: Abl2:cortactin interactions regulate dendritic spine stability via control of a stable filamentous actin pool.
5.00 nmol100ug Lyophilized100.00 ul10.00 nmol100ug Lyophilized2.50 nmol
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#33614634 2021/02/05
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Molecular Basis of LH Action on Breast Cancer Cell Migration and Invasion via Kinase and Scaffold Proteins.
Breast cancer (BC) is a major public health problem affecting women worldwide. Approximately 80% of diagnosed cases are hormone-dependent breast cancers. These hormones are known to stimulate tumor development and progression. In this setting, tentative evidence suggests that luteinizing hormone (LH) may also play a role in tumors. In BC cells that express functional LH receptors (LHR), this hormone regulates cell migration and invasion by controlling several kinases that activate actin cytoskeletal proteins. In this article, we show that LH induces phosphorylation of paxillin and its translocation toward the plasmatic membrane, where focal adhesion complexes are assembled. This process is triggered via a rapid extra-gonadal LHR signaling to Src/FAK/paxillin, which results in the phosphorylation/activation of the nucleation promoter factors cortactin and N-WASP. As a consequence, Arp2/3 complexes induce actin polymerization, essential to promote cell adhesion, migration, and invasion, thus enhancing metastatic spread of tumoral cells. Our findings provide relevant information about how gonadotrophins exert their action in BC. This information helps us understand the extragonadal effects of LH on BC metastasis. It may provide new perspectives for therapeutic treatment, especially for women with high serum levels of gonadotrophins.Joselina Magali Mondaca, Ivonne Denise Uzair, Ana Carla Castro Guijarro, Marina Inés Flamini, Angel Matias Sanchez
1265 related Products with: Molecular Basis of LH Action on Breast Cancer Cell Migration and Invasion via Kinase and Scaffold Proteins.
100ul20100ul5 x 10A5 cells/vial75IU100IU100ug10 mg
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#33600951 2021/02/16
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Podosome formation in the murine palatal mucosae: Its proteolytic role in rete peg formation.
Basement membrane remodeling is an indispensable factor for oral mucosal rete peg formation, but how the basement membrane is remodeled remains unclear. Our previous study indicated that keratinocyte growth factor induces the assembly of podosomes, which are dynamic organelles critical for matrix remodeling in human immortalized oral epithelial cells. This study explores podosome formation and its role in basement membrane remodeling during murine oral mucosal rete peg formation.Heng Chen, Lin Li, Sangang He, Guoliang Sa
2546 related Products with: Podosome formation in the murine palatal mucosae: Its proteolytic role in rete peg formation.
100 UG1100μg2 Pieces/Box
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#33548596 2021/02/03
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Recruitment of Polarity Complexes and Tight Junction Proteins to the Site of Apical Bulk Endocytosis.
The molecular motor, Myosin Vb (MYO5B), is well documented for its role in trafficking cargo to the apical membrane of epithelial cells. Despite its involvement in regulating apical proteins, the role of MYO5B in cell polarity is less clear. Inactivating mutations in MYO5B result in microvillus inclusion disease (MVID), a disorder characterized by loss of key apical transporters and the presence of intracellular inclusions in enterocytes. We previously identified that inclusions in Myo5b knockout (KO) mice form from invagination of the apical brush border via apical bulk endocytosis. Herein, we sought to elucidate the role of polarity complexes and tight junction proteins during the formation of inclusions.Amy C Engevik, Evan S Krystofiak, Izumi Kaji, Anne R Meyer, Victoria G Weis, Anna Goldstein, Alexander W Coutts, Tamene Melkamu, Milena Saqui-Salces, James R Goldenring
1987 related Products with: Recruitment of Polarity Complexes and Tight Junction Proteins to the Site of Apical Bulk Endocytosis.
1mg1mg501 mg101mg 5 G51mg20
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#33474679 2021/01/20
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Heregulin-induced cell migration is prevented by trastuzumab and trastuzumab-emtansine in HER2+ breast cancer.
Heregulin (HRG) signaling has been implicated in the development of an aggressive phenotype in breast cancer (BC) cells, and HER2 overexpression has been associated with a worse prognosis in BC patients. Nevertheless, the molecular mechanisms through which HRG affects the efficiency of anti-HER2 therapies such as trastuzumab (Tz) and trastuzumab-emtansine (T-DM1) are currently unknown.Joselina Magali Mondaca, Ana Carla Castro Guijarro, Marina Inés Flamini, Angel Matias Sanchez
1956 related Products with: Heregulin-induced cell migration is prevented by trastuzumab and trastuzumab-emtansine in HER2+ breast cancer.
100ug Lyophilized100ug Lyophilized100 ul
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#33466191 //
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Identification of potential biomarkers of peripheral blood mononuclear cell in hepatocellular carcinoma using bioinformatic analysis: A protocol for systematic review and meta-analysis.
Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis.Jin-Lin Peng, Ji-Zhou Wu, Guo-Jian Li, Jian-Lin Wu, Yu-Mei Xi, Xiao-Qing Li, Lei Wang
2754 related Products with: Identification of potential biomarkers of peripheral blood mononuclear cell in hepatocellular carcinoma using bioinformatic analysis: A protocol for systematic review and meta-analysis.
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#33407452 2021/01/06
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Profiling the expression of pro-metastatic genes in association with the clinicopathological features of primary breast cancer.
Metastasis accounts for ninety percent of breast cancer (BrCa) mortality. Cortactin, Ras homologous gene family member A (RhoA), and Rho-associated kinase (ROCK) raise cellular motility in favor of metastasis. Claudins (CLDN) belong to tight junction integrity and are dysregulated in BrCa. Thus far, epidemiologic evidence regarding the association of different pro-metastatic genes with pathological phenotypes of BrCa is largely inconsistent. This study aimed to determine the possible transcriptional models of pro-metastatic genes incorporate in holding the integrity of epithelial cell-cell junctions (CTTN, RhoA, ROCK, CLDN-1, CLDN-2, and CLDN-4), for the first time, in association with clinicopathological features of primary BrCa.Seyed-Mohammad Mazloomi, Mitra Foroutan-Ghaznavi, Vahid Montazeri, Gholamreza Tavoosidana, Ashraf Fakhrjou, Hojjatollah Nozad-Charoudeh, Saeed Pirouzpanah
2756 related Products with: Profiling the expression of pro-metastatic genes in association with the clinicopathological features of primary breast cancer.
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#33375626 2020/12/25
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Chaperone-Assisted Mitotic Actin Remodeling by BAG3 and HSPB8 Involves the Deacetylase HDAC6 and Its Substrate Cortactin.
The fidelity of actin dynamics relies on protein quality control, but the underlying molecular mechanisms are poorly defined. During mitosis, the cochaperone BCL2-associated athanogene 3 (BAG3) modulates cell rounding, cortex stability, spindle orientation, and chromosome segregation. Mitotic BAG3 shows enhanced interactions with its preferred chaperone partner HSPB8, the autophagic adaptor p62/SQSTM1, and HDAC6, a deacetylase with cytoskeletal substrates. Here, we show that depletion of BAG3, HSPB8, or p62/SQSTM1 can recapitulate the same inhibition of mitotic cell rounding. Moreover, depletion of either of these proteins also interfered with the dynamic of the subcortical actin cloud that contributes to spindle positioning. These phenotypes were corrected by drugs that limit the Arp2/3 complex or HDAC6 activity, arguing for a role for BAG3 in tuning branched actin network assembly. Mechanistically, we found that cortactin acetylation/deacetylation is mitotically regulated and is correlated with a reduced association of cortactin with HDAC6 in situ. Remarkably, BAG3 depletion hindered the mitotic decrease in cortactin-HDAC6 association. Furthermore, expression of an acetyl-mimic cortactin mutant in BAG3-depleted cells normalized mitotic cell rounding and the subcortical actin cloud organization. Together, these results reinforce a BAG3's function for accurate mitotic actin remodeling, via tuning cortactin and HDAC6 spatial dynamics.Carole Luthold, Alice-Anaïs Varlet, Herman Lambert, François Bordeleau, Josée N Lavoie
1150 related Products with: Chaperone-Assisted Mitotic Actin Remodeling by BAG3 and HSPB8 Involves the Deacetylase HDAC6 and Its Substrate Cortactin.
1 mg5mg1,000 tests100 mg100ug1000 tests100ug25 mg2.5 mg10 mg
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#33329350 2020/11/30
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Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management.
Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction, characterized by skeletal muscle weakness and fatigability. It is caused by autoantibodies targeting proteins of the neuromuscular junction; ~85% of MG patients have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 5% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). In the remaining about 10% of patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG). Since serological tests are relatively easy and non-invasive for disease diagnosis, the improvement of methods for the detection of known autoantibodies or the discovery of novel autoantibody specificities to diminish SN-MG and to facilitate differential diagnosis of similar diseases, is crucial. Radioimmunoprecipitation assays (RIPA) are the staple for MG antibody detection, but over the past years, using cell-based assays (CBAs) or improved highly sensitive RIPAs, it has been possible to detect autoantibodies in previously SN-MG patients. This led to the identification of more patients with antibodies to the classical antigens AChR and MuSK and to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets, such as agrin, K1.4 potassium channels, collagen Q, titin, the ryanodine receptor and cortactin have been found in some MG patients. Since the autoantigen targeted determines in part the clinical manifestations, prognosis and response to treatment, serological tests are not only indispensable for initial diagnosis, but also for monitoring treatment efficacy. Importantly, knowing the autoantibody profile of MG patients could allow for more efficient personalized therapeutic approaches. Significant progress has been made over the past years toward the development of antigen-specific therapies, targeting only the specific immune cells or autoantibodies involved in the autoimmune response. In this review, we will present the progress made toward the development of novel sensitive autoantibody detection assays, the identification of new MG autoantigens, and the implications for improved antigen-specific therapeutics. These advancements increase our understanding of MG pathology and improve patient quality of life by providing faster, more accurate diagnosis and better disease management.Konstantinos Lazaridis, Socrates J Tzartos