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https://www.readbyqxmd.com/read/29920238/effects-of-gm1-on-brain-spectrin-aminophospholipid-interactions
#1
Sauvik Sarkar, Dipayan Bose, Rajendra P Giri, Mrinmay K Mukhopadhyay, Abhijit Chakrabarti
Spectrin, a major component of the membrane skeletal meshwork of metazoan cells, is implicated to associate with membrane domains and is known to act as a scaffold for stabilization and activation of different signalling modules. We have studied the effect of GM1 (monosialotetrahexosyl ganglioside), a well-known model ganglioside and a signalling moiety, on the interaction of non-erythroid brain spectrin with both saturated and unsaturated aminophospholipids by spectroscopic methods. We observe that GM1 modulates brain spectrin-aminophospholipid interaction to the greatest degree whereas its effect on erythroid spectrin is not as pronounced...
June 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29907663/reorganization-of-destabilized-nodes-of-ranvier-in-%C3%AE-iv-spectrin-mutants-uncovers-critical-timelines-for-nodal-restoration-and-prevention-of-motor-paresis
#2
Julia Saifetiarova, Qian Shi, Martin Paukert, Masayuki Komada, Manzoor A Bhat
Disorganization of nodes of Ranvier is associated with motor and sensory dysfunctions. Mechanisms that allow nodal recovery during pathological processes remain poorly understood. A highly enriched nodal cytoskeletal protein βIV Spectrin anchors and stabilizes the nodal complex to actin cytoskeleton. Loss of murine βIV Spectrin allows the initial nodal organization, but causes gradual nodal destabilization. Mutations in human βIV SPECTRIN cause auditory neuropathy and impairment in motor coordination and similar phenotypes are caused by nodal disruption due to demyelination...
June 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29901439/tenectin-recruits-integrin-to-stabilize-bouton-architecture-and-regulate-vesicle-release-at-the-drosophila-neuromuscular-junction
#3
Qi Wang, Tae Hee Han, Peter Nguyen, Michal Jarnik, Mihaela Serpe
Assembly, maintenance and function of synaptic junctions depend on extracellular matrix (ECM) proteins and their receptors. Here we report that Tenectin (Tnc), a Mucin-type protein with RGD motifs, is an ECM component required for the structural and functional integrity of synaptic specializations at the neuromuscular junction (NMJ) in Drosophila. Using genetics, biochemistry, electrophysiology, histology and electron microscopy, we show that Tnc is secreted from motor neurons and striated muscles and accumulates in the synaptic cleft...
June 14, 2018: ELife
https://www.readbyqxmd.com/read/29891078/recessive-ataxias
#4
Matthis Synofzik, Andrea H Németh
Recessive ataxias (spinocerebellar ataxias, recessive or SCARs) are a heterogeneous group of rare, mostly neurodegenerative genetic disorders which usually start in childhood or early adult life. They can be subdivided into two major groups: predominant sensory or afferent ataxias, which are disorders mainly of the peripheral input to the cerebellum, and predominant cerebellar ataxias, in which the cerebellum is primarily affected. Next-generation sequencing technology has enabled the identification of >100 novel SCAR genes in the last 5 years, although most of them are ultrarare...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29884876/anti-band-3-and-anti-spectrin-antibodies-are-increased-in-plasmodium-vivax-infection-and-are-associated-with-anemia
#5
Luiza Carvalho Mourão, Rodrigo de Paula Baptista, Zélia Barbosa de Almeida, Priscila Grynberg, Maíra Mazzoni Pucci, Thiago Castro-Gomes, Cor Jesus Fernandes Fontes, Sumit Rathore, Yagya D Sharma, Rosiane A da Silva-Pereira, Marcelo Porto Bemquerer, Érika Martins Braga
Clearance of non-infected red blood cells (nRBCs) is one of the main components of anemia associated with Plasmodium vivax malaria. Recently, we have shown that anemic patients with P. vivax infection had elevated levels of anti-RBCs antibodies, which could enhance in vitro phagocytosis of nRBCs and decrease their deformability. Using immunoproteomics, here we characterized erythrocytic antigens that are differentially recognized by autoantibodies from anemic and non-anemic patients with acute vivax malaria...
June 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29879119/a-neuronal-map-kinase-constrains-growth-of-a-c-elegans-sensory-dendrite-throughout-the-life-of-the-organism
#6
Ian G McLachlan, Isabel Beets, Mario de Bono, Maxwell G Heiman
Neurons develop elaborate morphologies that provide a model for understanding cellular architecture. By studying C. elegans sensory dendrites, we previously identified genes that act to promote the extension of ciliated sensory dendrites during embryogenesis. Interestingly, the nonciliated dendrite of the oxygen-sensing neuron URX is not affected by these genes, suggesting it develops through a distinct mechanism. Here, we use a visual forward genetic screen to identify mutants that affect URX dendrite morphogenesis...
June 7, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29875650/the-actin-spectrin-membrane-associated-periodic-skeleton-in-neurons
#7
REVIEW
Nicolas Unsain, Fernando D Stefani, Alfredo Cáceres
Neurons are the most asymmetric cell types, with their axons commonly extending over lengths that are thousand times longer than the diameter of the cell soma. Fluorescence nanoscopy has recently unveiled that actin, spectrin and accompanying proteins form a membrane-associated periodic skeleton (MPS) that is ubiquitously present in mature axons from all neuronal types evaluated so far. The MPS is a regular supramolecular protein structure consisting of actin "rings" separated by spectrin tetramer "spacers"...
2018: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29867516/on-the-effects-of-reactive-oxygen-species-and-nitric-oxide-on-red-blood-cell-deformability
#8
Lukas Diederich, Tatsiana Suvorava, Roberto Sansone, T C Stevenson Keller, Frederik Barbarino, Thomas R Sutton, Christian M Kramer, Wiebke Lückstädt, Brant E Isakson, Holger Gohlke, Martin Feelisch, Malte Kelm, Miriam M Cortese-Krott
The main function of red blood cells (RBCs) is the transport of respiratory gases along the vascular tree. To fulfill their task, RBCs are able to elastically deform in response to mechanical forces and, pass through the narrow vessels of the microcirculation. Decreased RBC deformability was observed in pathological conditions linked to increased oxidative stress or decreased nitric oxide (NO) bioavailability, like hypertension. Treatments with oxidants and with NO were shown to affect RBC deformability ex vivo , but the mechanisms underpinning these effects are unknown...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29862265/a-review-on-adducin-from-functional-to-pathological-mechanisms-future-direction-in-cancer
#9
REVIEW
Karrie Mei-Yee Kiang, Gilberto Ka-Kit Leung
Adducin (ADD) is a family of membrane skeleton proteins including ADD1, ADD2, and ADD3 that are encoded by distinct genes on different chromosomes. Adducin is primarily responsible for the assembly of spectrin-actin network that provides physical support to the plasma membrane and mediates signal transduction in various cellular physiological processes upon regulation by protein kinase C-dependent and calcium/calmodulin-dependent pathways. Abnormal phosphorylation, genetic variations, and alternative splicing of adducin may contribute to alterations in cellular functions involved in pathogenic processes...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29861105/%C3%AE-iv-spectrinopathies-cause-profound-intellectual-disability-congenital-hypotonia-and-motor-axonal-neuropathy
#10
Chih-Chuan Wang, Xilma R Ortiz-González, Sabrina W Yum, Sara M Gill, Amy White, Erin Kelter, Laurie H Seaver, Sansan Lee, Graham Wiley, Patrick M Gaffney, Klaas J Wierenga, Matthew N Rasband
βIV spectrin links ankyrinG (AnkG) and clustered ion channels at axon initial segments (AISs) and nodes of Ranvier to the axonal cytoskeleton. Here, we report bi-allelic pathogenic SPTBN4 variants (three homozygous and two compound heterozygous) that cause a severe neurological syndrome that includes congenital hypotonia, intellectual disability, and motor axonal and auditory neuropathy. We introduced these variants into βIV spectrin, expressed these in neurons, and found that 5/7 were loss-of-function variants disrupting AIS localization or abolishing phosphoinositide binding...
June 7, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29805718/potential-alzheimer-s-disease-therapeutics-among-weak-cysteine-protease-inhibitors-exhibit-mechanistic-differences-regarding-extent-of-cathepsin-b-up-regulation-and-ability-to-block-calpain
#11
Heather Romine, Katherine M Rentschler, Kaitlan Smith, Ayanna Edwards, Camille Colvin, Karen Farizatto, Morgan C Pait, David Butler, Ben A Bahr
Cysteine protease inhibitors have long been part of drug discovery programs for Alzheimer's disease (AD), traumatic brain injury (TBI), and other disorders. Select inhibitors reduce accumulating proteins and AD pathology in mouse models. One such compound, Z-Phe-Aladiazomethylketone (PADK), exhibits a very weak IC50 (9-11 μM) towards cathepsin B (CatB), but curiously PADK causes marked up-regulation of the Aβ-degrading CatB and improves spatial memory. Potential therapeutic and weak inhibitor E64d (14 μM IC50 ) also up-regulates CatB...
October 2017: European Scientific Journal
https://www.readbyqxmd.com/read/29803115/grl1-protein-is-a-candidate-k-antigen-in-tetrahymena-thermophila
#12
Takahide Ota
In Tetrahymena, K antigens associate only with mature basal bodies and are expected to play important roles in the morphogenesis and function of the membrane skeleton around basal bodies, but these proteins have not been identified and their functions are unknown. Commercially available anti-human Rho GDP-dissociation inhibitor α (RhoGDIα) antibody (sc-33201) was accidentally found to show very similar immunofluorescence staining patterns to those of anti-K antigen antibodies, such as 424A8 and 10D12 mouse monoclonal antibodies, in Tetrahymena...
March 27, 2018: Protist
https://www.readbyqxmd.com/read/29802406/spectrin-is-a-mechanoresponsive-protein-shaping-fusogenic-synapse-architecture-during-myoblast-fusion
#13
Rui Duan, Ji Hoon Kim, Khurts Shilagardi, Eric S Schiffhauer, Donghoon M Lee, Sungmin Son, Shuo Li, Claire Thomas, Tianzhi Luo, Daniel A Fletcher, Douglas N Robinson, Elizabeth H Chen
Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage. Here, we report that α/βH -spectrin (βH is also called karst) dynamically accumulates and dissolves at the fusogenic synapse between fusing Drosophila muscle cells, where an attacking fusion partner invades its receiving partner with actin-propelled protrusions to promote cell fusion. Using genetics, cell biology, biophysics and mathematical modelling, we demonstrate that spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse...
June 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29790927/syntrophin-binds-directly-to-multiple-spectrin-like-repeats-in-dystrophin-and-mediates-binding-of-nnos-to-repeats-16-17
#14
Marvin E Adams, Guy L Odom, Min Jeong Kim, Jeffrey S Chamberlain, Stanley C Froehner
Mutation of the gene encoding dystrophin leads to Duchenne and Becker muscular dystrophy (DMD and BMD). Currently, dystrophin is thought to function primarily as a structural protein, connecting the muscle cell actin cytoskeleton to the extra-cellular matrix. In addition to this structural role, dystrophin also plays an important role as a scaffold that organizes an array of signaling proteins including sodium, potassium, and calcium channels, kinases, and nitric oxide synthase (nNOS). Many of these signaling proteins are linked to dystrophin via syntrophin, an adapter protein that is known to bind directly to two sites in the carboxyl terminal region of dystrophin...
May 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29784648/mouse-models-of-nesprin-related-diseases
#15
REVIEW
Can Zhou, Li Rao, Derek T Warren, Catherine M Shanahan, Qiuping Zhang
Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UNC84) domain-containing proteins at the nuclear envelope, in association with lamin A/C and emerin, linking the nucleoskeleton to the cytoskeleton. The LINC complex serves as both a physical linker between the nuclear lamina and the cytoskeleton and a mechanosensor. The LINC complex has a broad range of functions and is involved in maintaining nuclear architecture, nuclear positioning and migration, and also modulating gene expression...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29776093/impact-of-hydrodynamic-interactions-on-protein-folding-rates-depends-on-temperature
#16
Fabio C Zegarra, Dirar Homouz, Yossi Eliaz, Andrei G Gasic, Margaret S Cheung
We investigated the impact of hydrodynamic interactions (HI) on protein folding using a coarse-grained model. The extent of the impact of hydrodynamic interactions, whether it accelerates, retards, or has no effect on protein folding, has been controversial. Together with a theoretical framework of the energy landscape theory (ELT) for protein folding that describes the dynamics of the collective motion with a single reaction coordinate across a folding barrier, we compared the kinetic effects of HI on the folding rates of two protein models that use a chain of single beads with distinctive topologies: a 64-residue α/β chymotrypsin inhibitor 2 (CI2) protein, and a 57-residue β-barrel α-spectrin Src-homology 3 domain (SH3) protein...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29768467/alpha-7-nicotinic-receptors-attenuate-neurite-development-through-calcium-activation-of-calpain-at-the-growth-cone
#17
Justin R King, Nadine Kabbani
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth...
2018: PloS One
https://www.readbyqxmd.com/read/29749636/axon-initial-segments-structure-function-and-disease
#18
REVIEW
Claire Yu-Mei Huang, Matthew N Rasband
The axon initial segment (AIS) is located at the proximal axon and is the site of action potential initiation. This reflects the high density of ion channels found at the AIS. Adaptive changes to the location and length of the AIS can fine-tune the excitability of neurons and modulate plasticity in response to activity. The AIS plays an important role in maintaining neuronal polarity by regulating the trafficking and distribution of proteins that function in somatodendritic or axonal compartments of the neuron...
May 11, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29740886/atomic-force-microscopy-study-of-red-blood-cell-membrane-nanostructure-during-oxidation-reduction-processes
#19
E Kozlova, A Chernysh, V Sergunova, O Gudkova, E Manchenko, A Kozlov
The morphology and functional state of red blood cells (RBCs) mainly depends on the configuration of the spectrin network, which can be broken under the influence of intoxication because of oxidation processes in the cells. Measurement of these processes is a complex problem. The most suitable and prospective method that resolves this problem is atomic force microscopy (AFM). We used AFM to study the changes in the spectrin matrix and RBC morphology during oxidation processes caused by ultraviolet (UV) irradiation in RBC suspension...
May 8, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29739876/the-actin-cytoskeleton-of-the-mouse-sperm-flagellum-is-organized-in-a-helical-structure
#20
María Gracia Gervasi, Xinran Xu, Blanca Carbajal-Gonzalez, Mariano G Buffone, Pablo E Visconti, Diego Krapf
Conception of a new mammalian organism is determined by the fusion of a sperm cell with an oocyte during fertilization. Motility is one of the features of sperm that allows them to succeed in fertilization, and their flagellum is essential for this function. Longitudinally, the flagellum divides into the midpiece, the principal piece, and the end piece. A precise cytoskeletal architecture of the sperm tail is key for the acquisition of fertilization competence. It has been proposed that the actin cytoskeleton plays essential roles in the regulation of sperm motility, however, actin organization in sperm remains elusive...
May 8, 2018: Journal of Cell Science
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