The motor head of kinesin carries out microtubule binding, ATP hydrolysis, and force generation. Despite a high level of sequence and structural conservation, subtle variations in subdomains of the motor head determine family-specific properties. In particular, both Kinesin-1 (Kin-1) and Kinesin-5 (Kin-5) walk processively to the microtubule plus-end, yet show distinct motility characteristics suitable for their functions. We studied chimeric Kin-1/Kin-5 constructs with a combination of single molecule motility assays and molecular dynamics simulations to demonstrate that Kin-5 possesses a force-generating element similar to Kin-1, i.e., the cover-neck bundle. Furthermore, the Kin-5 neck linker makes additional contacts with the core of the motor head via loop L13, which putatively compensates for the shorter cover-neck bundle of Kin-5. Our results indicate that Kin-1 is mechanically optimized for individual cargo transport, whereas Kin-5 does not necessarily maximize its mechanical performance. Its biochemical rates and enhanced force sensitivity may instead be beneficial for operation in a group of motors. Such variations in subdomains would be a strategy for achieving diversity in motility with the conserved motor head.
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http://dx.doi.org/10.1016/j.bpj.2013.03.051 | DOI Listing |
Lancet Neurol
February 2025
Department of Neurosciences, and Leuven Brain Institute, University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, Center for Brain & Disease Research, VIB, Leuven, Belgium. Electronic address:
Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.
View Article and Find Full Text PDFPflugers Arch
January 2025
Division of Neurophysiology, Department of Physiology, Hyogo Medical University, Hyogo, 663 8501, Japan.
The nucleus tractus solitarius (NTS) contains neurons that relay sensory swallowing commands information from the oropharyngeal cavity and swallowing premotor neurons of the dorsal swallowing group (DSG). However, the spatio-temporal dynamics of the interplay between the sensory relay and the DSG is not well understood. Here, we employed fluorescence imaging after microinjection of the calcium indicator into the NTS in an arterially perfused brainstem preparation of rat (n = 8) to investigate neuronal population activity in the NTS in response to superior laryngeal nerve (SLN) stimulation.
View Article and Find Full Text PDFJ Integr Neurosci
January 2025
Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy.
The complicated neurological syndrome known as multiple sclerosis (MS) is typified by demyelination, inflammation, and neurodegeneration in the central nervous system (CNS). Managing this crippling illness requires an understanding of the complex interactions between neurophysiological systems, diagnostic techniques, and therapeutic methods. A complex series of processes, including immunological dysregulation, inflammation, and neurodegeneration, are involved in the pathogenesis of MS.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Agricultural & Rural Pollution Abatement and Environmental Safety, College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642, China.
Cadmium (Cd) pollution poses an important problem, but limited information is available about the toxicology effects of Cd on freshwater invertebrates. We investigated the accumulation, oxidative stress, microbial community changes, and transcriptomic alterations in apple snails ) under Cd stress. The snails were exposed to the 10 μg/L Cd solution for 16 days, followed by a 16-day elimination period.
View Article and Find Full Text PDFChildren (Basel)
December 2024
Faculty of Medicine, University Titu Maiorescu, 040441 Bucharest, Romania.
Our research aimed to assess if correlations could be found between items evaluated at the cerebral ultrasound performed at term-equivalent age (TEA) and neuro-motor outcomes evaluated at 12 and 24 months of corrected age in a group of preterm infants. The following were assessed: the Levine Index, the diagonals of the lateral ventricles, the size of the ventricular midbody, the sinocortical distance, the width of the basal ganglia, the cortical depth at the level of the cingular sulcus and the maturation of the gyral folding. The neurologic evaluation was performed at 12 and 24 months of corrected age, according to the Amiel Tison neurologic examination, and the items from the calendar of motor acquisitions were used as outcome measures of the study-gross and fine motor subsets.
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