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Muhammad-Zawwad Raza, Simone Allegrini, Charles Dumontet, Lars Petter Jordheim
Development of an organ and subsequently the whole system from an embryo is a highly integrated process. Although there is evidence that different systems are interconnected during developmental stages, the molecular understanding of this relationship is either not known or only to a limited extent. Nervous system development, amongst all, is maybe the most crucial and complex process. It relies on the correct distribution of specific neuronal growth factors and hormones to the specific receptors. Among the plethora of proteins that are involved in downstream signalling of neuronal growth factors, we find the kinase-D interacting substrate of 220 kDa (KIDINS220), also known as ankyrin-rich repeat membrane spanning (ARMS) protein...
March 2018: Genes, Chromosomes & Cancer
Kenichi Sakamoto, Toshihiko Imamura, Takuyo Kanayama, Mio Yano, Daisuke Asai, Takao Deguchi, Yoshiko Hashii, Akihiko Tanizawa, Yusei Ohshima, Nobutaka Kiyokawa, Keizo Horibe, Atsushi Sato
Although "paired box 5" (PAX5)-related fusion genes are well documented in childhood B-cell precursor acute lymphoblastic leukemia (ALL), these types of fusion with the exception of PAX5-JAK2 are rarely seen in patients with gene expression profiles similar to those of BCR-ABL1 (Philadelphia)-positive ALL (Ph-like ALL). We report a novel fusion of the genes PAX5 and "kinase D-interacting substrate of 220 kDa" (KIDINS220, also known as ARMS) in a Ph-like ALL. As PAX5 is a master regulator of B-lymphocyte differentiation, PAX5 rearrangements induce a differentiation block in B lymphocytes...
April 2017: Genes, Chromosomes & Cancer
Thorsten M Kranz, Adam Berns, Jerry Shields, Karen Rothman, Julie Walsh-Messinger, Raymond R Goetz, Moses V Chao, Dolores Malaspina
BACKGROUND: Rare gene variants are important sources of schizophrenia vulnerability that likely interact with polygenic susceptibility loci. This study examined if novel or rare missense coding variants in any of four different signaling genes in sporadic schizophrenia cases were associated with clinical phenotypes in an exceptionally well-characterized sample. METHOD: Structured interviews, cognition, symptoms and life course features were assessed in 48 ethnically-diverse cases with psychosis who underwent targeted exome sequencing of PTPRG (Protein Tyrosine Phosphatase, Receptor Type G), SLC39A13 (Solute Carrier Family 39 (Zinc Transporter) Member 13), TGM5 (transglutaminase 5) and ARMS/KIDINS220 (Ankyrin repeat-rich membrane spanning protein or Kinase D-Interacting Substrate of 220kDa)...
April 2016: EBioMedicine
Joachim Scholz-Starke, Fabrizia Cesca
The correct functioning of the nervous system depends on the exquisitely fine control of neuronal excitability and synaptic plasticity, which relies on an intricate network of protein-protein interactions and signaling that shapes neuronal homeostasis during development and in adulthood. In this complex scenario, Kinase D interacting substrate of 220 kDa/ankyrin repeat-rich membrane spanning (Kidins220/ARMS) acts as a multi-functional scaffold protein with preferential expression in the nervous system. Engaged in a plethora of interactions with membrane receptors, cytosolic signaling components and cytoskeletal proteins, Kidins220/ARMS is implicated in numerous cellular functions including neuronal survival, neurite outgrowth and maturation and neuronal activity, often in the context of neurotrophin (NT) signaling pathways...
2016: Frontiers in Cellular Neuroscience
Dragana J Josifova, Glen R Monroe, Federico Tessadori, Esther de Graaff, Bert van der Zwaag, Sarju G Mehta, Magdalena Harakalova, Karen J Duran, Sanne M C Savelberg, Isaäc J Nijman, Heinz Jungbluth, Casper C Hoogenraad, Jeroen Bakkers, Nine V Knoers, Helen V Firth, Philip L Beales, Gijs van Haaften, Mieke M van Haelst
We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally regulated in the brain. Molecular analysis of patients' variants confirmed expression and translation of truncated transcripts similar to recently characterized alternative terminal exon splice isoforms of KIDINS220 KIDINS220 undergoes extensive alternative splicing in specific neuronal populations and developmental time points, reflecting its complex role in neuronal maturation...
June 1, 2016: Human Molecular Genetics
Saray López-Benito, Concepción Lillo, Ángel Hernández-Hernández, Moses V Chao, Juan C Arévalo
Proper development of the nervous system requires a temporally and spatially orchestrated set of events including differentiation, synapse formation and neurotransmission. Nerve growth factor (NGF) acting through the TrkA neurotrophin receptor (also known as NTRK1) regulates many of these events. However, the molecular mechanisms responsible for NGF-regulated secretion are not completely understood. Here, we describe a new signaling pathway involving TrkA, ARMS (also known as Kidins220), synembryn-B and Rac1 in NGF-mediated secretion in PC12 cells...
May 1, 2016: Journal of Cell Science
Dolores Malaspina, Thorsten M Kranz, Adriana Heguy, Sheila Harroch, Robert Mazgaj, Karen Rothman, Adam Berns, Sumya Hasan, Daniel Antonius, Raymond Goetz, Mariana Lazar, Moses V Chao, Oded Gonen
Schizophrenia is a genetically complex syndrome with substantial inter-subject variability in multiple domains. Person-specific measures to resolve its heterogeneity could focus on the variability in prefrontal integrity, which this study indexed as relative rostralization within the anterior cingulate cortex (ACC). Twenty-two schizophrenia cases and 11 controls underwent rigorous diagnostic procedures, symptom assessments (PANSS, Deficit Syndrome Scale) and intelligence testing. All underwent multivoxel MRSI at 3T to measure concentrations of the neuronal-specific biomarker N-acetylaspartate (NAA) in all of the voxels of the ACC...
April 2016: Schizophrenia Research
A Gamir-Morralla, C López-Menéndez, S Ayuso-Dolado, G S Tejeda, J Montaner, A Rosell, T Iglesias, M Díaz-Guerra
Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), has a central role in the coordination of receptor crosstalk and the integration of signaling pathways essential for neuronal differentiation, survival and function. This protein is a shared downstream effector for neurotrophin- and ephrin-receptors signaling that also interacts with the N-methyl-d-aspartate type of glutamate receptors (NMDARs). Failures in neurotrophic support and glutamate signaling are involved in pathologies related to excitotoxicity and/or neurodegeneration, where different components of these dynamic protein complexes result altered by a combination of mechanisms...
2015: Cell Death & Disease
Gina J Fiala, Iga Janowska, Fabiola Prutek, Elias Hobeika, Annyesha Satapathy, Adrian Sprenger, Thomas Plum, Maximilian Seidl, Jörn Dengjel, Michael Reth, Fabrizia Cesca, Tilman Brummer, Susana Minguet, Wolfgang W A Schamel
B cell antigen receptor (BCR) signaling is critical for B cell development and activation. Using mass spectrometry, we identified a protein kinase D-interacting substrate of 220 kD (Kidins220)/ankyrin repeat-rich membrane-spanning protein (ARMS) as a novel interaction partner of resting and stimulated BCR. Upon BCR stimulation, the interaction increases in a Src kinase-independent manner. By knocking down Kidins220 in a B cell line and generating a conditional B cell-specific Kidins220 knockout (B-KO) mouse strain, we show that Kidins220 couples the BCR to PLCγ2, Ca(2+), and extracellular signal-regulated kinase (Erk) signaling...
September 21, 2015: Journal of Experimental Medicine
Nathalie Schmieg, Claire Thomas, Arisa Yabe, David S Lynch, Teresa Iglesias, Probir Chakravarty, Giampietro Schiavo
Kidins220/ARMS is a transmembrane protein playing a crucial role in neuronal and cardiovascular development. Kidins220/ARMS is a downstream target of neurotrophin receptors and interacts with several signalling and trafficking factors. Through computational modelling, we found two potential sites for alternative splicing of Kidins220/ARMS. The first is located between exon 24 and exon 29, while the second site replaces exon 32 by a short alternative terminal exon 33. Here we describe the conserved occurrence of several Kidins220/ARMS splice isoforms at RNA and protein levels...
2015: PloS One
Fabrizia Cesca, Annyesha Satapathy, Enrico Ferrea, Thierry Nieus, Fabio Benfenati, Joachim Scholz-Starke
Kidins220 (kinase D-interacting substrate of 220 kDa)/ankyrin repeat-rich membrane spanning (ARMS) acts as a signaling platform at the plasma membrane and is implicated in a multitude of neuronal functions, including the control of neuronal activity. Here, we used the Kidins220(-/-) mouse model to study the effects of Kidins220 ablation on neuronal excitability. Multielectrode array recordings showed reduced evoked spiking activity in Kidins220(-/-) hippocampal networks, which was compatible with the increased excitability of GABAergic neurons determined by current-clamp recordings...
July 17, 2015: Journal of Biological Chemistry
Vir B Singh, Alicia K Wooten, Joseph W Jackson, Sanjay B Maggirwar, Michelle Kiebala
Long-term persistence of human immunodeficiency virus type-1 (HIV) in the central nervous system (CNS) results in mild to severe neurocognitive impairment in a significant proportion of the HIV-infected population. These neurological deficits are known as HIV-associated neurocognitive disorders (HAND). Microglia are CNS-resident immune cells that are directly infected by HIV and consequently secrete proinflammatory molecules that contribute to HIV-induced neuroinflammation. Indeed, the number of activated macrophage and microglia in the brain is more highly correlated with cognitive impairment than the amount of neuronal apoptosis...
April 2015: Journal of Neurovirology
Heekyung Jung, Joo-Hyun Shin, Young-Seok Park, Mi-Sook Chang
Cell proliferation is tightly controlled by the cell-cycle regulatory proteins, primarily by cyclins and cyclin-dependent kinases (CDKs) in the G1 phase. The ankyrin repeat-rich membrane spanning (ARMS) scaffold protein, also known as kinase D-interacting substrate of 220 kDa (Kidins 220), has been previously identified as a prominent downstream target of neurotrophin and ephrin receptors. Many studies have reported that ARMS/Kidins220 acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems...
December 31, 2014: Molecules and Cells
Xiuqin Ni, Xing Li, Shuhua Tao, Minghui Xu, Hongmei Ma, Xiuli Wang
Ankyrin repeat-rich membrane spanning protein (ARMS), also known as kinase D-interacting substrate of 220 kDa (Kidins220), is a transmembrane protein that has been reported to be involved in the pathogenesis of asthma through the nerve growth factor (NGF)/tyrosine kinase A (TrkA) receptor signaling pathway. To investigate whether NGF/TrkA-Kidins220/ARMS-extracellular signal-regulated kinase (ERK) signaling is activated in airway inflammation of asthma, BALB/c mice were sensitized and challenged with ovalbumin (OVA)...
July 2013: Biomedical Reports
Silvia Marracci, Marianna Giannini, Marianna Vitiello, Massimiliano Andreazzoli, Luciana Dente
Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin Repeat-rich Membrane Spanning) is a conserved scaffold protein that acts as a downstream substrate for protein kinase D and mediates multiple receptor signalling pathways. Despite the dissecting of the function of this protein in mammals, using both in vitro and in vivo studies, a detailed characterization of its gene expression during early phases of embryogenesis has not been described yet. Here, we have used Xenopus laevis as a vertebrate model system to analyze the gene expression and the protein localization of Kidins220/ARMS...
2013: International Journal of Developmental Biology
Helen E Scharfman, Moses V Chao
A major problem in the field of neurodegeneration is the basis of selective vulnerability of subsets of neurons to disease. In aging, Alzheimer's disease (AD), and other disorders such as temporal lobe epilepsy, the superficial layers of the entorhinal cortex (EC) are an area of selective vulnerability. In AD, it has been suggested that the degeneration of these neurons may play a role in causing the disease because it occurs at an early stage. Therefore, it is important to define the distinctive characteristics of the EC that make this region particularly vulnerable...
2013: Cognitive Neuroscience
Ning Li, Xu Dong, Chang Yang, Yuli Liu, Xiuqin Ni
Nerve growth factor (NGF), combined with the high-affinity tyrosine kinase receptor A (TrkA), has been reported to be involved in the pathogenesis of asthma. Ankyrin-rich membrane spanning/transmembrane substrate of protein kinase D (ARMS/Kidins220), a TrkA‑binding protein, modulates the NGF signaling pathway. The aim of the present study was to investigate the expression of Kidins220/ARMS and the effect NGF has on the protein in the spleen and peripheral blood, following airway allergen challenge in mice...
December 2013: Molecular Medicine Reports
Danny A Rogers, Nina F Schor
BACKGROUND: Neurotrophic signaling is an important factor in the survival of developing neurons, and the expression of neurotrophic receptors correlates with prognosis in neuroblastoma. Kinase D-interacting substrate of 220 kDa (Kidins220) associates with neurotrophic receptors and stabilizes them, but the expression and function of Kidins220 in neuroblastoma are unknown. METHODS: We study Kidins220 expression in human neuroblastoma cell lines and tumor samples by western blotting and microarray analyses...
November 2013: Pediatric Research
Sumit Deswal, Anja Meyer, Gina J Fiala, Anja E Eisenhardt, Lisa C Schmitt, Mogjiborahman Salek, Tilman Brummer, Oreste Acuto, Wolfgang W A Schamel
The activation kinetics of MAPK Erk are critical for T cell development and activation. In particular, sustained Erk signaling is required for T cell activation and effector functions, such as IL-2 production. Although Raf-1 triggers transient Erk activation, B-Raf is implicated in sustained Erk signaling after TCR stimulation. In this study, we show that B-Raf is dephosphorylated on its inhibitory serine 365 upon TCR triggering. However, it is unknown how B-Raf activation is coupled to the TCR. Using mass spectrometry, we identified protein kinase D-interacting substrate of 220 kDa (Kidins220)/ankyrin repeat-rich membrane spanning protein, mammalian target of rapamycin, Rictor, Dock2, and GM130 as novel B-Raf interaction partners...
March 1, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
Danny A Rogers, Nina F Schor
Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns...
March 10, 2013: Experimental Cell Research
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