scholarly journals Pathogenic mutations in the kinesin-3 motor KIF1A diminish force generation and movement through allosteric mechanisms

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Breane G. Budaitis ◽  
Shashank Jariwala ◽  
Lu Rao ◽  
Yang Yue ◽  
David Sept ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Neurodevelopmental Disorders ◽  
Force Generation ◽  
Long Distance ◽  
Long Distance Transport ◽  
Cargo Transport ◽  
Dynamics Simulations ◽  
Run Lengths ◽  
Allosteric Mechanisms ◽  
Distance Transport

The kinesin-3 motor KIF1A functions in neurons, where its fast and superprocessive motility facilitates long-distance transport, but little is known about its force-generating properties. Using optical tweezers, we demonstrate that KIF1A stalls at an opposing load of ~3 pN but more frequently detaches at lower forces. KIF1A rapidly reattaches to the microtubule to resume motion due to its class-specific K-loop, resulting in a unique clustering of force generation events. To test the importance of neck linker docking in KIF1A force generation, we introduced mutations linked to human neurodevelopmental disorders. Molecular dynamics simulations predict that V8M and Y89D mutations impair neck linker docking. Indeed, both mutations dramatically reduce the force generation of KIF1A but not the motor’s ability to rapidly reattach to the microtubule. Although both mutations relieve autoinhibition of the full-length motor, the mutant motors display decreased velocities, run lengths, and landing rates and delayed cargo transport in cells. These results advance our understanding of how mutations in KIF1A can manifest in disease.

scholarly journals Pathogenic Mutations in the Kinesin-3 Motor KIF1A Diminish Force Generation and Movement Through Allosteric Mechanisms

2020 ◽  
Author(s):  
Breane G. Budaitis ◽  
Shashank Jariwala ◽  
Lu Rao ◽  
David Sept ◽  
Kristen J. Verhey ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Motor Domain ◽  
Force Generation ◽  
Long Distance ◽  
C Elegans ◽  
Long Distance Transport ◽  
Dynamics Simulations ◽  
Run Lengths ◽  
Allosteric Mechanisms ◽  
Kinesin Superfamily

ABSTRACTThe kinesin-3 motor KIF1A functions in neurons where its fast and superprocessive motility is thought to be critical for long-distance transport. However, little is known about the force-generating properties of kinesin-3 motors. Using optical tweezers, we demonstrate that KIF1A and its C. elegans homolog UNC-104 undergo force-dependent detachments at ~3 pN and then rapidly reattach to the microtubule to resume motion, resulting in a sawtooth pattern of clustered force generation events that is unique among the kinesin superfamily. Whereas UNC-104 motors stall before detaching, KIF1A motors do not. To examine the mechanism of KIF1A force generation, we introduced mutations linked to human neurodevelopmental disorders, V8M and Y89D, based on their location in structural elements required for force generation in kinesin-1. Molecular dynamics simulations predict that the V8M and Y89D mutations impair docking of the N-terminal (β9) or C-terminal (β10) portions of the neck linker, respectively, to the KIF1A motor domain. Indeed, both mutations dramatically impair force generation of KIF1A but not the motor’s ability to rapidly reattach to the microtubule track. Homodimeric and heterodimeric mutant motors also display decreased velocities, run lengths, and landing rates and homodimeric Y89D motors exhibit a higher frequency of non-productive, diffusive events along the microtubule. In cells, cargo transport by the mutant motors is delayed. Our work demonstrates the importance of the neck linker in the force generation of kinesin-3 motors and advances our understanding of how mutations in the kinesin motor domain can manifest in disease.

The Fine Structure of Phloem Cells

1985 ◽  
Vol 43 ◽  
pp. 632-635
Author(s):  
James Cronshaw
Keyword(s):  
Structural Studies ◽  
High Concentration ◽  
Long Distance ◽  
Phloem Tissue ◽  
Sieve Elements ◽  
Long Distance Transport ◽  
P Protein ◽  
Companion Cells ◽  
Electron Microscopical ◽  
Distance Transport

Long distance transport in plants takes place in phloem tissue which has characteristic cells, the sieve elements. At maturity these cells have sieve areas in their end walls with specialized perforations. They are associated with companion cells, parenchyma cells, and in some species, with transfer cells. The protoplast of the functioning sieve element contains a high concentration of sugar, and consequently a high hydrostatic pressure, which makes it extremely difficult to fix mature sieve elements for electron microscopical observation without the formation of surge artifacts. Despite many structural studies which have attempted to prevent surge artifacts, several features of mature sieve elements, such as the distribution of P-protein and the nature of the contents of the sieve area pores, remain controversial.

scholarly journals Comparative Analysis of Long-Distance Transportation with the Example of Sea and Rail Transport

Energies ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1689
Author(s):  
Tomasz Neumann
Keyword(s):  
Eastern China ◽  
Time Cost ◽  
Topsis Method ◽  
Long Distance ◽  
Long Distance Transport ◽  
The Subject ◽  
Transport Analysis ◽  
Multi Criteria Analysis ◽  
The Relationship ◽  
Distance Transport

The subject of the article is a comparative long-distance transport analysis based on the relationship between central and eastern China and Poland. It provides an overview of issues related to long-haul China–Poland. The technique for order of preference by similarity to ideal solution (TOPSIS) method was proposed in the multi-criteria analysis. This method was briefly discussed, and its choice was justified. Then, the criteria adopted in the analysis were presented, i.e., time, cost, maximum number of containers, and ecology index. Multi-criteria analysis was carried out for three cases: the transport of one loading unit, 82 loading units, and 200 loading units. The geopolitical and operational situation on the transport route for the analyzed modes of transport was discussed.

scholarly journals Selecting sorting centres to avoid long distance transport of weaned beef calves

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
T. Morel-Journel ◽  
E. Vergu ◽  
J.-B. Mercier ◽  
N. Bareille ◽  
P. Ezanno
Keyword(s):  
Negative Impact ◽  
Historical Record ◽  
Management Tool ◽  
Long Distance ◽  
Beef Calves ◽  
Long Distance Transport ◽  
And Performance ◽  
Distance Transport ◽  
French Beef ◽  
General Concern

AbstractThe transport of weaned calves from cow–calf producers to fatteners is a general concern for the young bull industry due to its documented negative impact on the welfare, health and performance of the animals. These transfers are often managed by intermediaries who transport weaned calves to sorting centres, where they are grouped into batches before being sent to fattening units. In this study, we present an algorithm to limiting these transfer distances by appropriately selecting the sorting centre through which they must go. We tested the effectiveness of this algorithm on historical data from a French beef producer organization managing 136,892 transfers using 13 sorting centres. The results show a decrease in the transfer distances compared to the historical record, especially for the calves travelling over long distances (− 76 km, i.e. 18% on average for the 33% longest transfers). Moreover, the distribution of calves between the sorting centres proposed by the algorithm reveals differences in their efficiency in minimizing transfer distances. In addition to its usefulness as a management tool for the daily transport of cattle, this algorithm provides prospects for improving the management of the sorting centres themselves.

Correlation of Grassy Lake and Cedar Lake ambers using infrared spectroscopy, stable isotopes, and palaeoentomology

2008 ◽  
Vol 45 (9) ◽  
pp. 1061-1082 ◽  
Author(s):  
Ryan C. McKellar ◽  
Alexander P. Wolfe ◽  
Ralf Tappert ◽  
Karlis Muehlenbachs
Keyword(s):  
Stable Isotopes ◽  
Fourier Transform ◽  
Infrared Spectroscopy ◽  
Late Cretaceous ◽  
Western Canada ◽  
Long Distance ◽  
Geochemical Fingerprinting ◽  
Long Distance Transport ◽  
Distance Transport

The Late Cretaceous Grassy Lake and Cedar Lake amber deposits of western Canada are among North America’s most famous amber-producing localities. Although it has been suggested for over a century that Cedar Lake amber from western Manitoba may be a secondary deposit having originated from strata in Alberta, this hypothesis has not been tested explicitly using geochemical fingerprinting coupled to comparative analyses of arthropod faunal content. Although there are many amber-containing horizons associated with Cretaceous coals throughout Alberta, most are thermally mature and brittle, thus lacking the resilience to survive long distance transport while preserving intact biotic inclusions. One of the few exceptions is the amber found in situ at Grassy Lake. We present a suite of new analyses from these and other Late Cretaceous ambers from western Canada, including stable isotopes (H and C), Fourier transform infrared (FTIR) spectra, and an updated faunal compendium for the Grassy and Cedar lakes arthropod assemblages. When combined with amber’s physical properties and stratigraphic constraints, the results of these analyses confirm that Cedar Lake amber is derived directly from the Grassy Lake amber deposit or an immediate correlative equivalent. This enables the palaeoenvironmental context of Grassy Lake amber to be extended to the Cedar Lake deposit, making possible a more inclusive survey of Cretaceous arthropod faunas.

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