scholarly journals Increased synaptic facilitation and exploratory behavior in mice lacking the presynaptic protein Mover

2019 ◽  
Author(s):  
Julio S. Viotti ◽  
Frederik W. Ott ◽  
Eva M. Schleicher ◽  
Jannek M. Wagner ◽  
Yvonne Bouter ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Special Functions ◽  
Reference Memory ◽  
Specific Protein ◽  
Molecular Machinery ◽  
Specific Proteins ◽  
Presynaptic Protein ◽  
Conserved Core ◽  
Presynaptic Proteins

AbstractIn vertebrates and invertebrates, neurotransmitter release relies on a highly conserved molecular machinery. A surprisingly small number of presynaptic proteins evolved specifically in vertebrates. How they expand the power or versatility of the conserved core machinery is unclear. One of these vertebrate-specific proteins, called Mover / TPRGL / SVAP30, is heterogeneously expressed throughout the brain, suggesting that it adds special functions to subtypes of presynaptic terminals. In this study we generated Mover knockout mice to investigate the role of Mover from synaptic transmission to behavior. Deletion of Mover did not affect synaptic transmission at CA3 to CA1 synapses. In contrast, Mover deficient mice had strongly increased short-term facilitation at mossy fiber to CA3 synapses. This increase included frequency facilitation, a hallmark of mossy fiber terminal function. The effect was age- and Ca2+-dependent, and relied on the Kainate receptor/cAMP pathway in the mossy fiber terminals. Despite this change in presynaptic plasticity, the absence of Mover did not affect long-term spatial reference memory or working memory, but led to reduced anxiety. These discoveries suggest that Mover has distinct roles at different synapses. At mossy-fiber terminals, it acts to constrain the extent of presynaptic facilitation. Its role in activity-dependent neurotransmission could be necessary for normal anxiety responses.Significance StatementThe enormous increase in the complexity of brains during evolution is accompanied by a remarkably small number of new, vertebrate-specific presynaptic proteins. These proteins are unlikely to be essential for transmitter release, because invertebrate synapses do not need them. But what functions do they fulfill? We show that the vertebrate-specific protein Mover is involved in constraining the release of neurotransmitters in some synapses in the hippocampus, while not affecting others. We further demonstrate that the absence of this protein leads to decreased anxiety levels. Understanding the function of such a protein can help us further understand synaptic transmission, the specializations that are brought about in vertebrate synapses, and how this can help or hinder neurological or psychiatric disorders.

scholarly journals Generation of asymmetry during development. Segregation of type-specific proteins in Caulobacter.

1979 ◽  
Vol 81 (1) ◽  
pp. 123-136 ◽  
Author(s):  
N Agabian ◽  
M Evinger ◽  
G Parker
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Messenger Rna ◽  
Cell Types ◽  
Specific Protein ◽  
Soluble Proteins ◽  
Specific Cell ◽  
Daughter Cells ◽  
Specific Proteins ◽  
Entire Cell

An essential event in developmental processes is the introduction of asymmetry into an otherwise undifferentiated cell population. Cell division in Caulobacter is asymmetric; the progeny cells are structurally different and follow different sequences of development, thus providing a useful model system for the study of differentiation. Because the progeny cells are different from one another, there must be a segregation of morphogenetic and informational components at some time in the cell cycle. We have examined the pattern of specific protein segregation between Caulobacter stalked and swarmer daughter cells, with the rationale that such a progeny analysis would identify both structurally and developmentally important proteins. To complement the study, we have also examined the pattern of protein synthesis during synchronous growth and in various cellular fractions. We show here, for the first time, that the association of proteins with a specific cell type may result not only from their periodicity of synthesis, but also from their pattern of distribution at the time of cell division. Several membrane-associated and soluble proteins are segregated asymmetrically between progeny stalked and swarmer cells. The data further show that a subclass of soluble proteins becomes associated with the membrane of the progeny stalked cells. Therefore, although the principal differentiated cell types possess different synthetic capabilities and characteristic proteins, the asymmetry between progeny stalked and swarmer cells is generated primarily by the preferential association of specific soluble proteins with the membrane of only one daughter cell. The majority of the proteins which exhibit this segregation behavior are synthesized during the entire cell cycle and exhibit relatively long, functional messenger RNA half-lives.

scholarly journals Photoreceptor Compartment-Specific TULP1 Interactomes

2021 ◽  
Author(s):  
Lindsey A Ebke ◽  
Satyabrata Sinha ◽  
Gayle JT Pauer ◽  
Stephanie A Hagstrom
Keyword(s):  
Molecular Motors ◽  
Protein Trafficking ◽  
Specific Interaction ◽  
Specific Protein ◽  
Vesicle Recycling ◽  
Binding Partners ◽  
Skeletal Protein ◽  
Liquid Chromatography Tandem Mass ◽  
In The Wild ◽  
Specific Proteins

Photoreceptors are highly compartmentalized cells with large amounts of proteins synthesized in the inner segment (IS) and transported to the outer segment (OS) and synaptic terminal. Tulp1 is a photoreceptor-specific protein localized to the IS and synapse. In the absence of Tulp1, sev-eral OS-specific proteins are mislocalized and synaptic vesicle recycling is impaired. To better understand the involvement of Tulp1 in protein trafficking, our approach was to physically iso-late Tulp1-containing photoreceptor compartments by serial tangential sectioning of retinas and to identify compartment-specific Tulp1 binding partners by immunoprecipitation followed by liquid chromatography tandem mass spectrometry. Our results indicate that Tulp1 has two dis-tinct interactomes. We report the identification of: 1) an IS-specific interaction between Tulp1 and the motor protein Kinesin family member 3a (Kif3a), 2) a synaptic-specific interaction be-tween Tulp1 and the scaffold protein Ribeye, and 3) an interaction between Tulp1 and the cyto-skeletal protein Microtubule-associated protein 1B (MAP1B) in both compartments. Immuno-localization studies in the wild-type retina indicate that Tulp1 and its binding partners co-localize to their respective compartments. Our observations are compatible with Tulp1 functioning in protein trafficking in multiple photoreceptor compartments, likely as an adapter molecule linking vesicles to molecular motors and the cytoskeletal scaffold.

scholarly journals Modular protein-oligonucleotide signal exchange

2020 ◽  
Vol 48 (12) ◽  
pp. 6431-6444
Author(s):  
Deepak K Agrawal ◽  
Rebecca Schulman
Keyword(s):  
Specific Protein ◽  
Vascular Endothelial ◽  
Complementary Dna ◽  
Exchange Processes ◽  
Dna Strand Displacement ◽  
Specific Proteins ◽  
Dna Strand ◽  
Endothelial Growth Factor ◽  
Signal Exchange

Abstract While many methods are available to measure the concentrations of proteins in solution, the development of a method to quantitatively report both increases and decreases in different protein concentrations in real-time using changes in the concentrations of other molecules, such as DNA outputs, has remained a challenge. Here, we present a biomolecular reaction process that reports the concentration of an input protein in situ as the concentration of an output DNA oligonucleotide strand. This method uses DNA oligonucleotide aptamers that bind either to a specific protein selectively or to a complementary DNA oligonucleotide reversibly using toehold-mediated DNA strand-displacement. It is possible to choose the sequence of output strand almost independent of the sensing protein. Using this strategy, we implemented four different exchange processes to report the concentrations of clinically relevant human α-thrombin and vascular endothelial growth factor using changes in concentrations of DNA oligonucleotide outputs. These exchange processes can operate in tandem such that the same or different output signals can indicate changes in concentration of distinct or identical input proteins. The simplicity of our approach suggests a pathway to build devices that can direct diverse output responses in response to changes in concentrations of specific proteins.

scholarly journals Plasma concentrations of platelet-specific proteins correlated with platelet survival

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 82-84 ◽  
Author(s):  
DJ Doyle ◽  
CN Chesterman ◽  
JF Cade ◽  
JR McGready ◽  
GC Rennie ◽  
...  
Keyword(s):  
Life Span ◽  
Plasma Concentrations ◽  
Specific Protein ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Platelet Survival ◽  
Specific Proteins ◽  
Artery Disease ◽  
Multiple Hit

Abstract Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.

scholarly journals Multiple mechanisms of dissociated epidermal cell spreading.

1983 ◽  
Vol 96 (1) ◽  
pp. 63-67 ◽  
Author(s):  
K S Stenn ◽  
J A Madri ◽  
T Tinghitella ◽  
V P Terranova
Keyword(s):  
Serum Albumin ◽  
Epidermal Cell ◽  
Type Iv Collagen ◽  
Cell Spreading ◽  
Specific Protein ◽  
Epidermal Cells ◽  
Type Iv ◽  
Basement Membrane Protein ◽  
Specific Proteins

To test the possibility that epidermal cells use a common basement membrane protein whenever they spread, in vitro experiments were conducted using trypsin-dissociated guinea pig epidermal cells and the following proteins: human serum, bovine serum albumin, serum fibronectin, Type IV collagen, laminin, and epibolin (a recently described serum glycoprotein which supports epidermal cell spreading; Stenn, K.S., 1981, Proc. Natl. Acad. Sci. U.S.A. 78:6907.). When the cells were added to media containing the specific proteins, all the tested proteins, except for serum albumin, supported cell spreading. Added to protein-coated substrates in defined media, the cells spread on fibronectin, epibolin, and laminin-Type IV collagen, but not on albumin or whole serum. In none of these experiments were the results qualitatively affected by the presence of cycloheximide. Antibodies to a specific protein blocked cell spreading on that protein but not on the other active proteins, e.g. whereas antibodies to epibolin blocked cell spreading on epibolin, they did not affect spreading on fibronectin, collagen, or laminin. In a second assay in which the cells were allowed to adhere to tissue culture plastic before the protein-containing medium was added, the cells spread only if the medium contained epibolin. Moreover, under these conditions the spreading activity of whole serum and plasma was neutralized by antiepibolin antibodies. These results support the conclusion that dissociated epidermal cells possess multiple spreading modes which depend, in part, on the proteins of the substrate, proteins of the medium, and the sequence of cell adhesion and protein exposure.

scholarly journals A Point Mutation in the Cargo-Binding Domain of Myosin V Affects Its Interaction with Multiple Cargoes

2005 ◽  
Vol 4 (4) ◽  
pp. 787-798 ◽  
Author(s):  
Natasha Pashkova ◽  
Natalie L. Catlett ◽  
Jennifer L. Novak ◽  
Lois S. Weisman
Keyword(s):  
Point Mutation ◽  
Specific Binding ◽  
Secretory Vesicle ◽  
Specific Protein ◽  
Myosin V ◽  
Specific Proteins ◽  
Tight Association ◽  
Vacuole Inheritance ◽  
Vesicle Movement ◽  
Cargo Binding

ABSTRACT Class V myosins move diverse intracellular cargoes, which attach via interaction of cargo-specific proteins to the myosin V globular tail. The globular tail of the yeast myosin V, Myo2p, contains two structural and functional subdomains. Subdomain I binds to the vacuole-specific protein, Vac17p, while subdomain II likely binds to an as yet unidentified secretory vesicle-specific protein. All functions of Myo2p require the tight association of subdomains I and II, which suggests that binding of a cargo to one subdomain may inhibit cargo-binding to a second subdomain. Thus, two types of mutations are predicted to specifically affect a subset of Myo2p cargoes: first are mutations within a cargo-specific binding region; second are mutations that mimic the inhibited conformation of one of the subdomains. Here we analyze a point mutation in subdomain I, myo2-2(G1248D), which is likely to be this latter type of mutation. myo2-2 has no effect on secretory vesicle movement. The secretory vesicle binding site is in subdomain II. However, myo2-2 is impaired in several Myo2p-related functions. While subdomains I and II of myo2-2p tightly associate, there are measurable differences in the conformation of its globular tail. Based solely on the ability to restore vacuole inheritance, a set of intragenic suppressors of myo2-2 were identified. All suppressor mutations reside in subdomain I. Moreover, subdomain I and II interactions occurred in all suppressors, demonstrating the importance of subdomain I and II association for Myo2p function. Furthermore, 3 of the 10 suppressors globally restored all tested defects in myo2-2. This large proportion of global suppressors strongly suggests that myo2-2(G1248) causes a conformational change in subdomain I that simultaneously affects multiple cargoes.

Immunological Identification of Organ Specific Proteins and Transcripts in Developing Barley Grains

1993 ◽  
Vol 48 (7-8) ◽  
pp. 609-615
Author(s):  
Helge Klungland ◽  
Marie Bosnes
Keyword(s):  
Specific Protein ◽  
Barley Grain ◽  
Starchy Endosperm ◽  
Sds Page ◽  
Organ Specific ◽  
Specific Proteins ◽  
Barley Grains ◽  
Immunological Identification

In vitro translated proteins from poly(A+)RNA of immature barley starchy endosperm and embryos were immunoadsorbed with antibodies raised against proteins of aleurone layers, starchy endosperm and embryos. Four starchy endosperm and eight embryo specific transcripts were detected. In addition, several mRNA s were restricted to only two of the three tis­sues.Comparing SDS-PAGE patterns of the in vivo protein extracts against which the antibodies were raised, four aleurone, six starchy endosperm and four embryo-specific protein bands were detectable. As for the in vitro translated proteins, several in vivo protein bands were here present in only two of the three tissues. Of eight known barley grain proteins for which antibodies were available, only three were present in developing embryos.

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