IKAP/hELP1 down-regulation in neuroblastoma cells causes enhanced cell adhesion mediated by contactin overexpression

Cohen-Kupiec, Rachel; Weinstein, Shiri; Kantor, Gal; Peer, Dan; Weil, Miguel

doi:10.4161/cam.4.4.12923

Cited by 4 publications

(13 citation statements)

References 35 publications

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“…2C ) and Contactin-associated protein4 ( Table S1 ) were expressed at higher levels. These results are consistent with the enhanced adhesion observed in IKAP-DR cells, which we have shown to be dependent on Contactin 1 [16] .…”

Section: Resultssupporting

confidence: 92%

“…Figure 1B shows IKAP protein expression of control and IKAP-DR cells at both NDF and DF growth conditions. Note that here too, IKAP expression is further reduced in both control and IKAP-DR cells in differentiation growth conditions, as reported previously [16] . The reduced expression of IKAP under differentiation is not related to the shRNA expression as it happens in control cells as well.…”

Section: Resultssupporting

confidence: 89%

“…Actin is a constituent of axonal growth cones [54] , [55] , [56] and the abnormal overexpression of actin-binding proteins in differentiation may cause aberrant actin distribution both in the cytoskeleton and in growth cones, which may lead to both migration and axonal growth problems. We and others have indeed recently shown that IKAP deficient SHSY5Y cells had abnormal looking neurite projections [16] .…”

Section: Discussionmentioning

confidence: 79%

“…The cell lines used in this study were described before [16]. Briefly, stable SHSY5Y cell lines were generated with IKBKAP shRNA TRCN0000037871 or with Control viruses carrying the pLKO.1-Puro control vector (Sigma) and were continually selected with 1 µg/ml puromycin (Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…SHSY5Y cells were grown in medium containing DMEM with glutamine (Gibco), 10% heat inactivated FCS (Hyclone), 2 mM sodium pyruvate (Invitrogen), and antibiotics (50 U/ml of penicillin, streptomycin and nystatin) (Biological Industries, Israel). The cell lines used in this study were described before [16] . Briefly, stable SHSY5Y cell lines were generated with IKBKAP shRNA TRCN0000037871 or with Control viruses carrying the pLKO.1-Puro control vector (Sigma) and were continually selected with 1 µg/ml puromycin (Sigma).…”

Section: Methodsmentioning

confidence: 99%

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Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

et al. 2011

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Familial dysautonomia (FD) is a developmental neuropathy of the sensory and autonomous nervous systems. The IKBKAP gene, encoding the IKAP/hELP1 subunit of the RNA polymerase II Elongator complex is mutated in FD patients, leading to a tissue-specific mis-splicing of the gene and to the absence of the protein in neuronal tissues. To elucidate the function of IKAP/hELP1 in the development of neuronal cells, we have downregulated IKBKAP expression in SHSY5Y cells, a neuroblastoma cell line of a neural crest origin. We have previously shown that these cells exhibit abnormal cell adhesion when allowed to differentiate under defined culture conditions on laminin substratum. Here, we report results of a microarray expression analysis of IKAP/hELP1 downregulated cells that were grown on laminin under differentiation or non-differentiation growth conditions. It is shown that under non-differentiation growth conditions, IKAP/hELP1 downregulation affects genes important for early developmental stages of the nervous system, including cell signaling, cell adhesion and neural crest migration. IKAP/hELP1 downregulation during differentiation affects the expression of genes that play a role in late neuronal development, in axonal projection and synapse formation and function. We also show that IKAP/hELP1 deficiency affects the expression of genes involved in calcium metabolism before and after differentiation of the neuroblastoma cells. Hence, our data support IKAP/hELP1 importance in the development and function of neuronal cells and contribute to the understanding of the FD phenotype.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

et al. 2011

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Metabolic Modulation of Cellular Function

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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Elongator promotes neuritogenesis via regulation of tau stability through acly activity

Shilian

Even²,

Gast³

et al. 2022

Front. Cell Dev. Biol.

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The six subunits (Elp1 to Elp6) Elongator complex promotes specific uridine modifications in tRNA’s wobble site. Moreover, this complex has been indirectly involved in the regulation of α-tubulin acetylation in microtubules (MTs) via the stabilization of ATP-Citrate Lyase (Acly), the main cytosolic source of acetyl-CoA production in cells, a key substrate used for global protein acetylation. Here, we report additional evidence that Elongator activity is important for proper cytoskeleton remodeling as cells lacking expression of Elp1 show morphology impairment; including distinct neurite process formation and disorganization and instability of MTs. Here, we show that loss of Elongator results in a reduction of expression of the microtubule associated protein Tau (MAPT). Tau, is a well-known key MT regulator in neurons whose lysines can be competitively acetylated or ubiquitylated. Therefore, we tested whether Tau is an indirect acetylation target of Elongator. We found that a reduction of Elongator activity leads to a decrease of lysine acetylation on Tau that favors its proteasomal degradation. This phenotype was prevented by using selective deacetylase or proteasomal inhibitors. Moreover, our data demonstrate that Acly’s activity regulates the mechanism underlying Tau mediated neurite morphology defects found in Elp1 KD since both Tau levels and neurites morphology are restored due to Acly overexpression. This suggests a possible involvement of both Tau and Acly dysfunction in Familial Dysautonomia (FD), which is an autosomal recessive peripheral neuropathy caused by mutation in the ELP1 gene that severely affects Elp1 expression levels in the nervous system in FD patients in a similar way as found previously in Elp1 KD neuroblastoma cells.

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IKAP/hELP1 down-regulation in neuroblastoma cells causes enhanced cell adhesion mediated by contactin overexpression

Cited by 4 publications

References 35 publications

Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

Metabolic Modulation of Cellular Function

Elongator promotes neuritogenesis via regulation of tau stability through acly activity

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