scholarly journals Mechanical Principles Governing the Shapes of Dendritic Spines

2021 ◽  
Vol 12 ◽  
Author(s):  
Haleh Alimohamadi ◽  
Miriam K. Bell ◽  
Shelley Halpain ◽  
Padmini Rangamani
Keyword(s):  
Dendritic Spines ◽  
Energy Landscape ◽  
Force Generation ◽  
Biophysical Model ◽  
Spine Shape ◽  
Postsynaptic Activity ◽  
Wide Range ◽  
Associated Proteins ◽  
Periodic Rings ◽  
Ring Structures

Dendritic spines are small, bulbous protrusions along the dendrites of neurons and are sites of excitatory postsynaptic activity. The morphology of spines has been implicated in their function in synaptic plasticity and their shapes have been well-characterized, but the potential mechanics underlying their shape development and maintenance have not yet been fully understood. In this work, we explore the mechanical principles that could underlie specific shapes using a minimal biophysical model of membrane-actin interactions. Using this model, we first identify the possible force regimes that give rise to the classic spine shapes—stubby, filopodia, thin, and mushroom-shaped spines. We also use this model to investigate how the spine neck might be stabilized using periodic rings of actin or associated proteins. Finally, we use this model to predict that the cooperation between force generation and ring structures can regulate the energy landscape of spine shapes across a wide range of tensions. Thus, our study provides insights into how mechanical aspects of actin-mediated force generation and tension can play critical roles in spine shape maintenance.

scholarly journals Mechanical principles governing the shapes of dendritic spines

2020 ◽  
Author(s):  
H. Alimohamadi ◽  
M.K. Bell ◽  
S. Halpain ◽  
P. Rangamani
Keyword(s):  
Dendritic Spines ◽  
Energy Landscape ◽  
Force Generation ◽  
Biophysical Model ◽  
Spine Shape ◽  
Postsynaptic Activity ◽  
Wide Range ◽  
Associated Proteins ◽  
Periodic Rings ◽  
Ring Structures

AbstractDendritic spines are small, bulbous protrusions along the dendrites of neurons and are sites of excitatory postsynaptic activity. The morphology of spines has been implicated in their function in synaptic plasticity and their shapes have been well-characterized, but the potential mechanics underlying their shape development and maintenance have not yet been fully understood. In this work, we explore the mechanical principles that could underlie specific shapes using a minimal biophysical model of membrane-actin interactions. Using this model, we first identify the possible force regimes that give rise to the classic spine shapes – stubby, filopodia, thin, and mushroom-shaped spines. We also use this model to investigate how the spine neck might be stabilized using periodic rings of actin or associated proteins. Finally, we use this model to predict that the cooperation between force generation and ring structures can regulate the energy landscape of spine shapes across a wide range of tensions. Thus, our study provides insights into how mechanical aspects of actin-mediated force generation and tension can play critical roles in spine shape maintenance.

scholarly journals Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Susan L. Brockmeier ◽  
Crystal L. Loving ◽  
Tracy L. Nicholson ◽  
Jinhong Wang ◽  
Sarah E. Peters ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Trial ◽  
Streptococcus Suis ◽  
Protein Subunit ◽  
Content Type ◽  
Degree Of Protection ◽  
Wide Range ◽  
Associated Proteins ◽  
Clinical Protection ◽  
Cellular Immune

ABSTRACT Streptococcus suis is a bacterium that is commonly carried in the respiratory tract and that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities, efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent S. suis . While subunit vaccination with the S. suis proteins induced IgG antibodies to each individual protein and a cellular immune response to the pool of proteins and provided substantial protection from challenge with virulent S. suis , the immune response elicited and the degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different S. suis serotypes, indicating a potential for cross protection.

scholarly journals Scale-dependent tipping points of bacterial colonization resistance

2021 ◽  
Author(s):  
Yuya Karita ◽  
David T Limmer ◽  
Oskar Hallatschek
Keyword(s):  
Bacterial Colonization ◽  
Biophysical Model ◽  
Tipping Points ◽  
Colonization Resistance ◽  
Wide Range ◽  
Colonization Success ◽  
Dental Cavities ◽  
The Stability ◽  
Cell Motion ◽  
Stability And Resilience

Bacteria are efficient colonizers of a wide range of secluded micro-habitats, such as soil pores, skin follicles, dental cavities or crypts in gut-like environments. Although numerous factors promoting or obstructing stable colonization have been identified, we currently lack systematic approaches to explore how population stability and resilience depend on the scale of the micro-habitat. Using a microfluidic device to grow bacteria in crypt-like incubation chambers of systematically varied lengths, we found that the incubation scale can sensitively tune bacterial colonization success and resistance against invaders. Small crypts are un-colonizable, intermediately sized crypts can stably support dilute populations, while beyond a second critical lengthscale, populations phase-separate into a dilute and a jammed region. We demonstrate that the jammed state confers extreme colonization resistance, even if the resident strain is suppressed by an antibiotic. Combined with a flexible biophysical model, we show that scale acts as an environmental filter that can be tuned via the competition between growth and collective cell motion. More broadly, our observations underscore that scale can profoundly bias experimental outcomes in microbial ecology. Systematic, flow-adjustable lengthscale variations may serve as a promising strategy to elucidate further scale-sensitive tipping points and to rationally modulate the stability and resilience of microbial colonizers.

Functional Contacts With a Range of Splicing Proteins Suggest a Central Role for Brr2p in the Dynamic Control of the Order of Events in Spliceosomes ofSaccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1451-1467 ◽  
Author(s):  
Rob W van Nues ◽  
Jean D Beggs
Keyword(s):  
Protein Interactions ◽  
Dynamic Control ◽  
Splicing Factors ◽  
Functional Protein ◽  
U6 Snrna ◽  
Wide Range ◽  
Snrnp Protein ◽  
Associated Proteins ◽  
Step Factor ◽  
Hybrid Screening

AbstractMapping of functional protein interactions will help in understanding conformational rearrangements that occur within large complexes like spliceosomes. Because the U5 snRNP plays a central role in pre-mRNA splicing, we undertook exhaustive two-hybrid screening with Brr2p, Prp8p, and other U5 snRNP-associated proteins. DExH-box protein Brr2p interacted specifically with five splicing factors: Prp8p, DEAH-box protein Prp16p, U1 snRNP protein Snp1p, second-step factor Slu7p, and U4/U6.U5 tri-snRNP protein Snu66p, which is required for splicing at low temperatures. Co-immunoprecipitation experiments confirmed direct or indirect interactions of Prp16p, Prp8p, Snu66p, and Snp1p with Brr2p and led us to propose that Brr2p mediates the recruitment of Prp16p to the spliceosome. We provide evidence that the prp8-1 allele disrupts an interaction with Brr2p, and we propose that Prp8p modulates U4/U6 snRNA duplex unwinding through another interaction with Brr2p. The interactions of Brr2p with a wide range of proteins suggest a particular function for the C-terminal half, bringing forward the hypothesis that, apart from U4/U6 duplex unwinding, Brr2p promotes other RNA rearrangements, acting synergistically with other spliceosomal proteins, including the structurally related Prp2p and Prp16p. Overall, these protein interaction studies shed light on how splicing factors regulate the order of events in the large spliceosome complex.

scholarly journals Evaluation by quantitative acid elution and radioimmunoassay of multiple classes of immunoglobulins and serum albumin associated with platelets in idiopathic thrombocytopenic purpura

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1126-1131 ◽  
Author(s):  
AJ Hotchkiss ◽  
CA Leissinger ◽  
ME Smith ◽  
JV Jordan ◽  
CA Kautz ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Solid Phase ◽  
Similar Group ◽  
Thrombocytopenic Purpura ◽  
Large Numbers ◽  
Wide Range ◽  
Platelet Concentration ◽  
Associated Proteins ◽  
Solid Phase Radioimmunoassay

Abstract Immunoglobulins (Igs) and serum albumin were eluted from normal platelets and platelets from patients with idiopathic thrombocytopenic purpura (ITP) with a quantitative acid elution procedure followed by solid-phase radioimmunoassay (SPRIA). Acid elution was shown to release a reproducible fraction of platelet-associated Igs, and the amounts released per platelet were independent of the platelet concentration over a wide range of concentrations. This procedure is suitable for sensitive, reproducible, and specific quantitation of large numbers of samples. Washed platelets from 13 normal donors contained the following components (expressed in femtograms per platelet, mean +/- 2 SEM): IgG, 1.40 +/- 0.26; IgA, 0.72 +/- 0.36; IgM 0.078 +/- 0.036; albumin 7.7 +/- 1.5. Immunoglobulins and albumin eluted from the platelets of ten ITP patients (two in remission), expressed as femtograms per platelet, mean (range), were: IgG 104 (0.3 to 750); IgA 90 (0.9 to 715); IgM 162 (1.2 to 1,300); and albumin 34 (6.8 to 199). All platelet-associated Igs from thrombocytopenic ITP patients were found to be elevated twofold to 2,300-fold with one Ig class occasionally elevated 50-fold to 100-fold higher than the others. A similar group of ten thrombocytopenic ITP patients was found to have twofold to 26-fold elevations of platelet- associated albumin. This demonstration of increases in multiple classes of Igs as well as serum albumin associated with platelets from ITP patients suggests that some nonimmune process may be contributing to the phenomenon of increased platelet-associated proteins in ITP.

Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing

2009 ◽  
Vol 102 (4) ◽  
pp. 2396-2409 ◽  
Author(s):  
Andrew M. Tan ◽  
Jin-Sung Choi ◽  
Stephen G. Waxman ◽  
Bryan C. Hains
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Synaptic Transmission ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Nociceptive Neurons ◽  
Spine Shape ◽  
Cord Injury ◽  
Dendritic Spine Morphology ◽  
Neuronal Signal

Central sensitization, a prolonged hyperexcitability of dorsal horn nociceptive neurons, is a major contributor to abnormal pain processing after spinal cord injury (SCI). Dendritic spines are micron-sized dendrite protrusions that can regulate the efficacy of synaptic transmission. Here we used a computational approach to study whether changes in dendritic spine shape, density, and distribution can individually, or in combination, adversely modify the input–output function of a postsynaptic neuron to create a hyperexcitable neuronal state. The results demonstrate that a conversion from thin-shaped to more mature, mushroom-shaped spine structures results in enhanced synaptic transmission and fidelity, improved frequency-following ability, and reduced inhibitory gating effectiveness. Increasing the density and redistributing spines toward the soma results in a greater probability of action potential activation. Our results demonstrate that changes in dendritic spine morphology, documented in previous studies on spinal cord injury, contribute to the generation of pain following SCI.

scholarly journals A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

2020 ◽  
Vol 17 (167) ◽  
pp. 20190866 ◽  
Author(s):  
Stefan Badelt ◽  
Casey Grun ◽  
Karthik V. Sarma ◽  
Brian Wolfe ◽  
Seung Woo Shin ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Biophysical Model ◽  
Kinetic Properties ◽  
Strand Displacement ◽  
Natural Connection ◽  
Dna Strand Displacement ◽  
Wide Range ◽  
Dna Strand ◽  
High Level ◽  
Domain Level

Information technologies enable programmers and engineers to design and synthesize systems of startling complexity that nonetheless behave as intended. This mastery of complexity is made possible by a hierarchy of formal abstractions that span from high-level programming languages down to low-level implementation specifications, with rigorous connections between the levels. DNA nanotechnology presents us with a new molecular information technology whose potential has not yet been fully unlocked in this way. Developing an effective hierarchy of abstractions may be critical for increasing the complexity of programmable DNA systems. Here, we build on prior practice to provide a new formalization of ‘domain-level’ representations of DNA strand displacement systems that has a natural connection to nucleic acid biophysics while still being suitable for formal analysis. Enumeration of unimolecular and bimolecular reactions provides a semantics for programmable molecular interactions, with kinetics given by an approximate biophysical model. Reaction condensation provides a tractable simplification of the detailed reactions that respects overall kinetic properties. The applicability and accuracy of the model is evaluated across a wide range of engineered DNA strand displacement systems. Thus, our work can serve as an interface between lower-level DNA models that operate at the nucleotide sequence level, and high-level chemical reaction network models that operate at the level of interactions between abstract species.

scholarly journals The structured core of human β tubulin confers isotype-specific polymerization properties

2016 ◽  
Vol 213 (4) ◽  
pp. 425-433 ◽  
Author(s):  
Melissa C. Pamula ◽  
Shih-Chieh Ti ◽  
Tarun M. Kapoor
Keyword(s):  
Dynamic Instability ◽  
Sequence Divergence ◽  
Regulatory Proteins ◽  
Microtubule Dynamic ◽  
Microtubule Associated Proteins ◽  
Cytoskeleton Organization ◽  
Wide Range ◽  
Associated Proteins ◽  
And Function ◽  
Β Tubulin

Diversity in cytoskeleton organization and function may be achieved through variations in primary sequence of tubulin isotypes. Recently, isotype functional diversity has been linked to a “tubulin code” in which the C-terminal tail, a region of substantial sequence divergence between isotypes, specifies interactions with microtubule-associated proteins. However, it is not known whether residue changes in this region alter microtubule dynamic instability. Here, we examine recombinant tubulin with human β isotype IIB and characterize polymerization dynamics. Microtubules with βIIB have catastrophe frequencies approximately threefold lower than those with isotype βIII, a suppression similar to that achieved by regulatory proteins. Further, we generate chimeric β tubulins with native tail sequences swapped between isotypes. These chimeras have catastrophe frequencies similar to that of the corresponding full-length construct with the same core sequence. Together, our data indicate that residue changes within the conserved β tubulin core are largely responsible for the observed isotype-specific changes in dynamic instability parameters and tune tubulin’s polymerization properties across a wide range.

scholarly journals Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Holly Stefen ◽  
Chanchanok Chaichim ◽  
John Power ◽  
Thomas Fath
Keyword(s):  
Actin Cytoskeleton ◽  
Neurological Diseases ◽  
Synaptic Function ◽  
Excitatory Synapses ◽  
Key Factors ◽  
Complex Interplay ◽  
Structure And Dynamics ◽  
Wide Range ◽  
Associated Proteins ◽  
Cytoskeletal Elements

Disruption of synaptic function at excitatory synapses is one of the earliest pathological changes seen in wide range of neurological diseases. The proper control of the segregation of neurotransmitter receptors at these synapses is directly correlated with the intact regulation of the postsynaptic cytoskeleton. In this review, we are discussing key factors that regulate the structure and dynamics of the actin cytoskeleton, the major cytoskeletal building block that supports the postsynaptic compartment. Special attention is given to the complex interplay of actin-associated proteins that are found in the synaptic specialization. We then discuss our current understanding of how disruption of these cytoskeletal elements may contribute to the pathological events observed in the nervous system under disease conditions with a particular focus on Alzheimer’s disease pathology.

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