scholarly journals The Regulatory Function of the AAA4 ATPase Domain of Cytoplasmic Dynein

2021 ◽  
Vol 120 (3) ◽  
pp. 163a
Author(s):  
Xinglei Liu ◽  
Lu Rao ◽  
Arne Gennerich
Keyword(s):  
Cytoplasmic Dynein ◽  
Regulatory Function ◽  
Atpase Domain

scholarly journals The regulatory function of the AAA4 ATPase domain of cytoplasmic dynein

2020 ◽  
Author(s):  
Xinglei Liu ◽  
Lu Rao ◽  
Arne Gennerich
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Essential Role ◽  
Cytoplasmic Dynein ◽  
Regulatory Function ◽  
Atpase Domain ◽  
Single Molecule Fluorescence ◽  
Mechanochemical Cycle ◽  
Aaa Atpases

AbstractCytoplasmic dynein is the primary motor for microtubule minus-end-directed transport and is indispensable to eukaryotic cells. Although each motor domain of dynein contains three active AAA+ ATPases (AAA1, 3, and 4), only the functions of AAA1 and 3 are known. Here, we use single-molecule fluorescence and optical tweezers studies to elucidate the role of AAA4 in dynein’s mechanochemical cycle. We demonstrate that AAA4 controls the priming stroke of the motion-generating linker, which connects the dimerizing tail of the motor to the AAA+ ring. Before ATP binds to AAA4, dynein remains incapable of generating motion. However, when AAA4 is bound to ATP, the gating of AAA1 by AAA3 prevails and dynein motion can occur. Thus, AAA1, 3, and 4 work together to regulate dynein function. Our work elucidates an essential role for AAA4 in dynein’s stepping cycle and underscores the complexity and crosstalk among the motor’s multiple AAA+ domains.

scholarly journals The regulatory function of the AAA4 ATPase domain of cytoplasmic dynein

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinglei Liu ◽  
Lu Rao ◽  
Arne Gennerich
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Essential Role ◽  
Cytoplasmic Dynein ◽  
Regulatory Function ◽  
Atpase Domain ◽  
Single Molecule Fluorescence ◽  
Mechanochemical Cycle ◽  
Aaa Atpases

AbstractCytoplasmic dynein is the primary motor for microtubule minus-end-directed transport and is indispensable to eukaryotic cells. Although each motor domain of dynein contains three active AAA+ ATPases (AAA1, 3, and 4), only the functions of AAA1 and 3 are known. Here, we use single-molecule fluorescence and optical tweezers studies to elucidate the role of AAA4 in dynein’s mechanochemical cycle. We demonstrate that AAA4 controls the priming stroke of the motion-generating linker, which connects the dimerizing tail of the motor to the AAA+ ring. Before ATP binds to AAA4, dynein remains incapable of generating motion. However, when AAA4 is bound to ATP, the gating of AAA1 by AAA3 prevails and dynein motion can occur. Thus, AAA1, 3, and 4 work together to regulate dynein function. Our work elucidates an essential role for AAA4 in dynein’s stepping cycle and underscores the complexity and crosstalk among the motor’s multiple AAA+ domains.

scholarly journals Structural basis for two-way communication between dynein and microtubules

2019 ◽  
Author(s):  
Noritaka Nishida ◽  
Yuta Komori ◽  
Osamu Takarada ◽  
Atsushi Watanabe ◽  
Satoko Tamura ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Conformational Changes ◽  
Structural Changes ◽  
Coiled Coil ◽  
Cytoplasmic Dynein ◽  
Structural Basis ◽  
Atpase Domain ◽  
Directional Bias ◽  
Α Helix ◽  
Half Turn

AbstractThe movements of cytoplasmic dynein on microtubule (MT) tracks is achieved by two-way communication between the microtubule-binding domain (MTBD) and the ATPase domain of dynein via an a-helical coiled-coil stalk, but the structural basis of this communication remains elusive. Here, we regulated MTBD either in high-affinity or low-affinity states by introducing a disulfide bond between the coiled-coils and analyzed the resulting structures by NMRand cryo-EM. In the MT-unbound state, the affinity changes of MTBD were achieved by sliding of the N-terminal α-helix by one half-turn, which suggests that structural changes propagate from the ATPase-domain to MTBD. In addition, cryo-EM analysis showed that MT binding induced further sliding of the N-terminal α-helix even without the disulfide bond, which suggests the MT-induced conformational changes propagate toward the ATPase domain. Based on differences in the MT-binding surface between the high- and low-affinity states, we propose a potential mechanism for the directional bias of dynein movement on MT tracks.

Microtubule Dynamics and Organelle Transport in Reticulomyxa

1990 ◽  
Vol 48 (3) ◽  
pp. 194-195
Author(s):  
Yih-Tai Chen ◽  
Ursula Euteneuer ◽  
Ken B. Johnson ◽  
Michael P. Koonce ◽  
Manfred Schliwa
Keyword(s):  
Plasma Membrane ◽  
Light Microscopy ◽  
Cytoplasmic Dynein ◽  
Living Cells ◽  
Microtubule Dynamics ◽  
Model Systems ◽  
Organelle Transport ◽  
Biochemical Characteristics ◽  
Dependent Transport

The application of video techniques to light microscopy and the development of motility assays in reactivated or reconstituted model systems rapidly advanced our understanding of the mechanism of organelle transport and microtubule dynamics in living cells. Two microtubule-based motors have been identified that are good candidates for motors that drive organelle transport: kinesin, a plus end-directed motor, and cytoplasmic dynein, which is minus end-directed. However, the evidence that they do in fact function as organelle motors is still indirect.We are studying microtubule-dependent transport and dynamics in the giant amoeba, Reticulomyxa. This cell extends filamentous strands backed by an extensive array of microtubules along which organelles move bidirectionally at up to 20 μm/sec (Fig. 1). Following removal of the plasma membrane with a mild detergent, organelle transport can be reactivated by the addition of ATP (1). The physiological, pharmacological and biochemical characteristics show the motor to be a cytoplasmic form of dynein (2).

Microtubule motors and other maps

1990 ◽  
Vol 48 (3) ◽  
pp. 1-1
Author(s):  
Richard B. Vallee
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Cytoplasmic Dynein ◽  
Organelle Transport ◽  
Structural Components ◽  
Microtubule Associated Proteins ◽  
Microtubule Motors ◽  
Associated Proteins ◽  
The Subject ◽  
Intracellular Motility

Microtubules are involved in a number of forms of intracellular motility, including mitosis and bidirectional organelle transport. Purified microtubules from brain and other sources contain tubulin and a diversity of microtubule associated proteins (MAPs). Some of the high molecular weight MAPs - MAP 1A, 1B, 2A, and 2B - are long, fibrous molecules that serve as structural components of the cytamatrix. Three MAPs have recently been identified that show microtubule activated ATPase activity and produce force in association with microtubules. These proteins - kinesin, cytoplasmic dynein, and dynamin - are referred to as cytoplasmic motors. The latter two will be the subject of this talk.Cytoplasmic dynein was first identified as one of the high molecular weight brain MAPs, MAP 1C. It was determined to be structurally equivalent to ciliary and flagellar dynein, and to produce force toward the minus ends of microtubules, opposite to kinesin.

Emotions Under the Skin

2015 ◽  
Vol 29 (4) ◽  
pp. 161-170 ◽  
Author(s):  
Catarina Silva ◽  
Ana Cláudia Ferreira ◽  
Isabel Soares ◽  
Francisco Esteves
Keyword(s):  
Attachment Style ◽  
Attachment Styles ◽  
The Other ◽  
Regulatory Function ◽  
Physiological Reactivity ◽  
Emotional Stimuli ◽  
Skin Conductance Responses ◽  
Lower Accuracy ◽  
Emotional Pictures ◽  
Valence And Arousal

Abstract. The present study examined physiological reactivity to emotional stimuli as a function of attachment style. Skin conductance responses (SCRs) and heart rate (HR) changes were simultaneously recorded while participants engaged in a visual attentional task. The task included positive, neutral, and negative emotional pictures, and required the identification of a target (neutral picture rotated 90° to the left or right), among a stream of pictures in which an emotional distracter (positive or negative) was presented. Participants additionally rated each of the emotional distracters for valence and arousal. Behavioral results on the attentional task showed that positive pictures facilitated overall target detection for all participants, compared to negative and neutral pictures, and that anxiously attached participants had significantly lower accuracy scores, relative to the other groups. Affective ratings indicated that positive pictures were rated as being more pleasant than negative ones, although no differences were found in HR changes to picture valence. In contrast, negative pictures were evaluated as being highly arousing. Consistent with this, negative pictures elicited larger SCRs in both insecure anxious and avoidant groups, especially for the anxious while the secure group showed SCRs unaffected by stimuli’s arousal. Present results show that individuals with different attachment styles reveal distinct patterns of attentional bias, appraisal, and physiological reactivity toward emotionally arousing stimuli. These findings further highlight the regulatory function of the attachment system.

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya
Keyword(s):  
Fatty Acids ◽  
Experimental Model ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Coconut Oil ◽  
The Body ◽  
Regulatory Function ◽  
Omega 3 ◽  
White Rats ◽  
Arachidonic Acids

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

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