Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM)

Leshchyns’ka, Iryna; Sytnyk, Vladimir

doi:10.1080/19490992.2015.1118194

Cited by 8 publications

(3 citation statements)

References 40 publications

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“…Two isoforms (140 kD and 180 kD) of NCAM show transmembrane binding and have intracellular domains while the 120 kD isoform has a glycosyl-phosphatidylinositol membrane anchor but no intracellular domains 38 . While the three isoforms have different C-termini, the N-terminal extracellular domains are identical in all three isoforms 39 . Therefore, we used the 120 kD isoform to test whether CD56 is directly interacting with A .…”

Section: Discussionmentioning

confidence: 99%

CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells

Ziegler

Weiß

Schmitt

et al. 2017

Sci Rep

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Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A. fumigatus we used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is re-organized and accumulated at this interaction site time-dependently. The inhibition of the cytoskeleton showed that the receptor re-organization was an active process dependent on actin re-arrangements. Furthermore, we could show that CD56 plays a role in the fungus mediated NK cell activation, since blocking of CD56 surface receptor reduced fungal mediated NK cell activation and reduced cytokine secretion. These results confirmed the direct interaction of NK cells and A. fumigatus, leading to the conclusion that CD56 is a pathogen recognition receptor. These findings give new insights into the functional role of CD56 in the pathogen recognition during the innate immune response.Invasive aspergillosis (IA), primarily caused by the mold Aspergillus fumigatus, is a devastating disease in immunocompromised patients suffering from hematological malignancies or undergoing allogeneic hematopoietic stem cell transplantation (HSCT) 1 . The mortality rate of HSCT patients diagnosed with IA ranges from 60-90% 2 and the prognosis for long-term survival is extremely poor 3 . Recently, it was shown that HSCT patients with probable/proven IA had a delayed reconstitution of natural killer (NK) cells for more than a year post HSCT 4 . In addition, patients with severe IA were found to have a lower NK cell count compared to patients with well-controlled IA, suggesting that NK cells play a critical role in immunity to IA.NK cells comprise 5-15% of the peripheral blood mononuclear cells (PBMCs) in healthy individuals and belong to the innate immune system 5 . Upon activation, NK cells release immune regulatory cytokines to stimulate other immune cells and display cytotoxicity directed against tumor or virus-infected cells by granule release 5 . NK cells are defined as CD56 positive and CD3 negative cells and can be distinguished into CD3 − CD56 dim CD16 + and CD3 − CD56 bright CD16 − cells. While CD56 dim cells are more cytotoxic, CD56 bright cells produce high levels of cytokines such as IFNγ and TNFα 6 . The function of NK cells is induced by the interplay of inhibitory and activating receptors 7 , leading to cytotoxicity directed against tumors and virus-infected cells. Besides the recognition of these cells, NK cells also recognize other infectious pathogens, become activated, and as a response induce either lysis of these pathogens or trigger activation of other...

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Section: Discussionmentioning

confidence: 99%

CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells

Ziegler

Weiß

Schmitt

et al. 2017

Sci Rep

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“…CD56 is a glycoprotein that exists on the surface of various cells and belongs to the immunoglobulin superfamily [ 23 ]. It plays a vital role in the growth and development of the nervous system as well as in facilitating cell–cell adhesion [ 24 , 25 ]. Additionally, CD56 can influence the infiltration, invasion and metastasis of malignant tumours [ 5 , 10 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/β-catenin signaling pathways in clear cell renal cell carcinoma

Jian,

Zhang,

Gong

et al. 2023

Cancer Cell Int

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Background CD56 has been observed in malignant tumours exhibiting neuronal or neuroendocrine differentiation, such as breast cancer, small-cell lung cancer, and neuroblastoma. Abnormal glycosylation modifications are thought to play a role in regulating tumour cell proliferation, migration, and invasion. Nevertheless, the exact roles and molecular mechanisms of CD56 and polysialylated CD56 (PSA-CD56) in the development and progression of clear cell renal cell carcinoma (ccRCC) remain elusive. Here we unveil the biological significance of CD56 and PSA-CD56 in ccRCC. Methods In this study, we employed various techniques, including immunohistochemistry (IHC), RT-qPCR, and western blot, to examine the mRNA and protein expression levels in both human ccRCC tissue and cell lines. Lentivirus infection and CRISPR/Cas9 system were utilized to generate overexpression and knockout cell lines of CD56. Additionally, we conducted several functional assays, such as CCK-8, colony formation, cell scratch, and transwell assays to evaluate cell growth, proliferation, migration, and invasion. Furthermore, we established a xenograft tumor model to investigate the role of CD56 in ccRCC in vivo. To gain further insights into the molecular mechanisms associated with CD56, we employed the Hedgehog inhibitor JK184 and the β-catenin inhibitor Prodigiosin. Results CD56 was significantly overexpressed in both human ccRCC tissues and renal cancer cell lines compared to adjacent normal tissues and normal renal epithelial cells. In vitro and in vivo experiments revealed that the knockout of CD56 inhibited the proliferation, migration, and invasion capabilities of ccRCC cells, whereas the overexpression of PSA-CD56 promoted these capacities. Finally, PSA-CD56 overexpression was found to activate both the Hedgehog and Wnt/β-catenin signaling pathways. Conclusion Our findings demonstrate that the oncogenic function of CD56 polysialylation plays a vital role in the tumorigenesis and progression of ccRCC, implying that targeting PSA-CD56 might be a feasible treatment target for ccRCC.

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“…NSE expression occurs when the PI3K and ERK signaling pathways, which are required for neurogenesis, are activated (Haque et al, 2018). In addition to these markers, neuronal nuclei (NeuN), a nuclear protein found in mature neurons, plays an important role in neuronal differentiation (Duan et al, 2016; Leshchyns'ka & Sytnyk, 2015).…”

Section: Introductionmentioning

confidence: 99%

Methods used to achieve different levels of the neuronal differentiation process in SH‐SY5Y and Neuro2a cell lines: An integrative review

dos Santos,

Gomes,

Costa

2023

Cell Biology International

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To study the process of neuronal differentiation, the human neuroblastoma (SH‐SY5Y) and the murine neuroblastoma (Neuro2a) cell lines have proven to be effective models. For this approach, different protocols involving known neurotrophic factors and other molecules, such as retinoic acid (RA), have been assessed to better understand the neuronal differentiation process. Thus, the goal of this manuscript was to provide a brief overview of recent studies that have used protocols to promote neurodifferentiation in SH‐SY5Y and Neuro2a cell lines and used acquired morphology and neuronal markers to validate whether differentiation was effective. The published results supply some guidance regarding the relationship between RA and neurotrophins for SH‐SY5Y, as well a serum concentrations for both cell lines. Furthermore, they demonstrate the potential application of Neuro2a, which is critical for future research on neuronal differentiation.

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Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM)

Cited by 8 publications

References 40 publications

CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells

CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/β-catenin signaling pathways in clear cell renal cell carcinoma

Methods used to achieve different levels of the neuronal differentiation process in SH‐SY5Y and Neuro2a cell lines: An integrative review

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