scholarly journals Non-invasive force measurement reveals the number of active kinesins on a synaptic vesicle precursor in axonal transport regulated by ARL-8

2018 ◽  
Vol 20 (5) ◽  
pp. 3403-3410 ◽  
Author(s):  
Kumiko Hayashi ◽  
Shin Hasegawa ◽  
Takashi Sagawa ◽  
Sohei Tasaki ◽  
Shinsuke Niwa

The regulatory role of ARL-8 in the number of motors carrying a cargo is revealed by non-invasive force measurement.

2020 ◽  
Author(s):  
Kumiko Hayashi ◽  
Miki G. Miyamoto ◽  
Shinsuke Niwa

AbstractSynaptic cargo transport by kinesin and dynein in hippocampal neurons was investigated using non-invasive measurements of transport force based on non-equilibrium statistical mechanics. Although direct physical measurements such as force measurement using optical tweezers are difficult in an intracellular environment, the non-invasive estimations enabled enumerating force producing units (FPUs) carrying a cargo comprising the motor proteins generating force. The number of FPUs served as a barometer for stable and long-distance transport by multiple motors, which was then used to quantify the extent of damage to axonal transport by dynarrestin, a dynein inhibitor. We found that dynarrestin decreased the FPU for retrograde transport more than anterograde transport. In the future, these measurements may be used to quantify the damage to axonal transport resulting from neuronal diseases including Alzheimer’s, Parkinson’s, and Huntington’s diseases.


2007 ◽  
Vol 18 (12) ◽  
pp. 5091-5099 ◽  
Author(s):  
Simon Rose ◽  
Maria Grazia Malabarba ◽  
Claudia Krag ◽  
Anna Schultz ◽  
Hanako Tsushima ◽  
...  

Intersectin is a multifunctional protein that interacts with components of the endocytic and exocytic pathways, and it is also involved in the control of actin dynamics. Drosophila intersectin is required for viability, synaptic development, and synaptic vesicle recycling. Here, we report the characterization of intersectin function in Caenorhabditis elegans. Nematode intersectin (ITSN-1) is expressed in the nervous system, and it is enriched in presynaptic regions. The C. elegans intersectin gene (itsn-1) is nonessential for viability. In addition, itsn-1-null worms do not display any evident phenotype, under physiological conditions. However, they display aldicarb-hypersensitivity, compatible with a negative regulatory role of ITSN-1 on neurotransmission. ITSN-1 physically interacts with dynamin and EHS-1, two proteins involved in synaptic vesicle recycling. We have previously shown that EHS-1 is a positive modulator of synaptic vesicle recycling in the nematode, likely through modulation of dynamin or dynamin-controlled pathways. Here, we show that ITSN-1 and EHS-1 have opposite effects on aldicarb sensitivity, and on dynamin-dependent phenotypes. Thus, the sum of our results identifies dynamin, or a dynamin-controlled pathway, as a potential target for the negative regulatory role of ITSN-1.


2017 ◽  
Author(s):  
Kumiko Hayashi ◽  
Yuta Tsuchizawa ◽  
Mitsuhiro Iwaki ◽  
Yasushi Okada

AbstractAlthough its importance is recently widely accepted, force measurement has been difficult in living biological systems, mainly due to the lack of the versatile non-invasive force measurement methods. The fluctuation theorem, which represents the thermodynamic properties of small fluctuating non-equilibrium systems, has been applied to the analysis of the thermodynamic properties of motor proteinsin vitro. Here, we extend it to the axonal transport (displacement) of endosomes. The distribution of the displacement fluctuation had three or four distinct peaks around multiples of a unit value, which the fluctuation theorem can convert into the drag force exerted on the endosomes. The results demonstrated that a single cargo vesicle is conveyed by one to three or four units of force production.


2014 ◽  
Author(s):  
Agnieszka Rak-Mardyla ◽  
Anna Wrobel ◽  
Eliza Drwal ◽  
Ewa Gregoraszczuk

2016 ◽  
Vol 1 (1) ◽  
pp. 4
Author(s):  
Marymol Koshy ◽  
Bushra Johari ◽  
Mohd Farhan Hamdan ◽  
Mohammad Hanafiah

Hypertrophic cardiomyopathy (HCM) is a global disease affecting people of various ethnic origins and both genders. HCM is a genetic disorder with a wide range of symptoms, including the catastrophic presentation of sudden cardiac death. Proper diagnosis and treatment of this disorder can relieve symptoms and prolong life. Non-invasive imaging is essential in diagnosing HCM. We present a review to deliberate the potential use of cardiac magnetic resonance (CMR) imaging in HCM assessment and also identify the risk factors entailed with risk stratification of HCM based on Magnetic Resonance Imaging (MRI).


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