Modeling Prion Transport in a Tunneling Nanotube

2013 ◽  
Author(s):  
Ivan A. Kuznetsov ◽  
Andrey V. Kuznetsov
Keyword(s):  
Analytical Solution ◽  
Transit Time ◽  
Molecular Motors ◽  
Population Model ◽  
Lateral Diffusion ◽  
Tunneling Nanotube ◽  
Myosin Va ◽  
Dependent Transport ◽  
Endocytic Vesicles

We develop a model for simulating prion transport in a tunneling nanotube (TNT). We simulate the situation when two cells, one of which is infected, are connected by a TNT. We consider two mechanisms of prion transport: lateral diffusion in the TNT membrane and active actin-dependent transport inside endocytic vesicles. Endocytic vesicles are propelled by myosin Va molecular motors. Since the transit time of prions through a TNT is short (several minutes), the two population model developed here assumes that there is no interchange between the two prion populations, and that partitioning between the prion populations is decided by prion loading at the TNT entrance. The split between the two prion populations at the TNT entrance is decided by the degree of loading, which indicates the portion of prions that enter a TNT in endocytic vesicles. An analytical solution describing prion concentrations and fluxes is obtained.

scholarly journals The kinesin superfamily protein KIF17: one protein with many functions

2012 ◽  
Vol 3 (3) ◽  
pp. 267-282 ◽  
Author(s):  
Margaret T.T. Wong-Riley ◽  
Joseph C. Besharse
Keyword(s):  
Molecular Motors ◽  
Coiled Coil ◽  
Intraflagellar Transport ◽  
Brain Regions ◽  
Sensory Cells ◽  
Tail Domain ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Chemosensory Perception ◽  
Dependent Transport

AbstractKinesins are ATP-dependent molecular motors that carry cargos along microtubules, generally in an anterograde direction. They are classified into 14 distinct families with varying structural and functional characteristics. KIF17 is a member of the kinesin-2 family that is plus end-directed. It is a homodimer with a pair of head motor domains that bind microtubules, a coiled-coil stalk, and a tail domain that binds cargos. In neurons, KIF17 transports N-methyl-D-aspartate receptor NR2B subunit, kainate receptor GluR5, and potassium Kv4.2 channels from cell bodies exclusively to dendrites. These cargos are necessary for synaptic transmission, learning, memory and other functions. KIF17’s interaction with nuclear RNS export factor 2 (NXF2) enables the transport of mRNA bidirectionally in dendrites. KIF17 or its homolog osmotic avoidance abnormal protein 3 (OSM-3) also mediates intraflagellar transport of cargos to the distal tips of flagella or cilia, thereby aiding in ciliogenesis. In many invertebrate and vertebrate sensory cells, KIF17 delivers cargos that contribute to chemosensory perception and signal transduction. In vertebrate photoreceptors, KIF17 is necessary for outer segment development and disc morphogenesis. In the testis, KIF17 (KIF17b) mediates microtubule-independent delivery of an activator of cAMP-responsive element modulator (ACT) from the nucleus to the cytoplasm and microtubule-dependent transport of Spatial-ε, both are presumably involved in spermatogenesis. KIF17 is also implicated in epithelial polarity and morphogenesis, placental transport and development, and the development of specific brain regions. The transcriptional regulation of Kif17 has recently been found to be mediated by nuclear respiratory factor 1 (NRF-1), which also regulates NR2B as well as energy metabolism in neurons. Dysfunctions of KIF17 are linked to a number of pathologies.

scholarly journals Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins

2018 ◽  
Author(s):  
Noura Alzahofi ◽  
Christopher L. Robinson ◽  
Tobias Welz ◽  
Emma L. Page ◽  
Deborah A. Briggs ◽  
...  
Keyword(s):  
Long Range ◽  
Animal Cells ◽  
Long Distance ◽  
Range Transport ◽  
Myosin Va ◽  
A Cell ◽  
Dependent Transport ◽  
Organelle Membrane ◽  
Assembly Proteins ◽  
Distance Transport

AbstractCell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that motor myosin-Va, works with dynamic actin tracks, to drive long-range organelle dispersion in microtubule depleted cells. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport. Here we show that SPIRE1/2 and formin-1 (FMN1) proteins generate actin tracks required for myosin-Va-dependent transport in melanocytes. Moreover we show that, in addition to melanophilin/myosin-Va, Rab27a can recruit SPIRE1/2 to melanosomes, thereby integrating motor and track assembly activity at the organelle membrane. Based on this we suggest a model in which organelles and force generators (motors and track assemblers) are linked forming a cell-wide network that allows their collective activity to rapidly disperse the population of organelles long-distance throughout the cytoplasm.

scholarly journals ATP-Citrate lyase fuels axonal transport across species

2020 ◽  
Author(s):  
Aviel Even ◽  
Giovanni Morelli ◽  
Romain Le Bail ◽  
Michal Shilian ◽  
Silvia Turchetto ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Motors ◽  
Recessive Mutation ◽  
Projection Neurons ◽  
Atp Citrate Lyase ◽  
Tubulin Acetylation ◽  
Gene Coding ◽  
Citrate Lyase ◽  
Autosomal Recessive Mutation ◽  
Dependent Transport

AbstractMicrotubule (MT)-based transport is an evolutionary conserved processed finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, which is catalyzed by the α-tubulin N-acetyltransferase 1, Atat1, promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanisms that controls Atat1 activity remains poorly understood. Here, we show that a pool of vesicular ATP-citrate lyase Acly acts as a rate limiting enzyme to modulate Atat1 activity by controlling availability of Acetyl-Coenzyme-A (Acetyl-CoA). In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in the pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine new light on the pathophysiological mechanisms underlying FD.

Oriented endocytic recycling of α5β1 in motile neutrophils

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2471-2480 ◽  
Author(s):  
Lynda M. Pierini ◽  
Moira A. Lawson ◽  
Robert J. Eddy ◽  
Bill Hendey ◽  
Frederick R. Maxfield
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Neutrophil Migration ◽  
Lateral Diffusion ◽  
Polymorphonuclear Neutrophils ◽  
Free Calcium ◽  
Endocytic Recycling ◽  
Free Calcium Concentration ◽  
Integrin Attachments ◽  
Endocytic Vesicles

Abstract During cell migration, integrin attachments to the substratum provide the means to generate the traction and force necessary to achieve locomotion. Once the cell has moved over these attachments, however, it is equally important that integrins detach from the substratum. The fate of integrins after detachment may include release from the cell, lateral diffusion across the cell surface, or endocytosis and redelivery to the cell surface. Polymorphonuclear neutrophils (PMNs) become stuck on the extracellular matrix proteins fibronectin and vitronectin when their intracellular free calcium concentration ([Ca++]i) is buffered. Taking advantage of this feature of PMN migration, we investigated the fate of integrins to differentiate among various models of migration. We demonstrate that 5β1, one of the fibronectin-binding integrins, is responsible for immobilization of [Ca++]i-buffered PMNs on fibronectin. We find that 5 and β1 are in endocytic vesicles in PMNs and that 5 colocalizes with a marker for an endocytic recycling compartment. When [Ca++]i is buffered, 5 and β1 become concentrated in clusters in the rear of the adherent cells, suggesting that [Ca++]i transients are required for 5β1 detachment from the substratum. Inhibition of 5β1 detachment by buffering [Ca++]i results in the depletion of 5 from both endocytic vesicles and the recycling compartment, providing compelling evidence that integrins are normally recycled by way of endocytosis and intracellular trafficking during cell migration. This model is further refined by our demonstration that the endocytic recycling compartment reorients to retain its localization just behind the leading lamella as PMNs migrate, indicating that membrane recycling during neutrophil migration has directionality.

Oriented endocytic recycling of α5β1 in motile neutrophils

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2471-2480 ◽  
Author(s):  
Lynda M. Pierini ◽  
Moira A. Lawson ◽  
Robert J. Eddy ◽  
Bill Hendey ◽  
Frederick R. Maxfield
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Neutrophil Migration ◽  
Lateral Diffusion ◽  
Polymorphonuclear Neutrophils ◽  
Free Calcium ◽  
Endocytic Recycling ◽  
Free Calcium Concentration ◽  
Integrin Attachments ◽  
Endocytic Vesicles

During cell migration, integrin attachments to the substratum provide the means to generate the traction and force necessary to achieve locomotion. Once the cell has moved over these attachments, however, it is equally important that integrins detach from the substratum. The fate of integrins after detachment may include release from the cell, lateral diffusion across the cell surface, or endocytosis and redelivery to the cell surface. Polymorphonuclear neutrophils (PMNs) become stuck on the extracellular matrix proteins fibronectin and vitronectin when their intracellular free calcium concentration ([Ca++]i) is buffered. Taking advantage of this feature of PMN migration, we investigated the fate of integrins to differentiate among various models of migration. We demonstrate that 5β1, one of the fibronectin-binding integrins, is responsible for immobilization of [Ca++]i-buffered PMNs on fibronectin. We find that 5 and β1 are in endocytic vesicles in PMNs and that 5 colocalizes with a marker for an endocytic recycling compartment. When [Ca++]i is buffered, 5 and β1 become concentrated in clusters in the rear of the adherent cells, suggesting that [Ca++]i transients are required for 5β1 detachment from the substratum. Inhibition of 5β1 detachment by buffering [Ca++]i results in the depletion of 5 from both endocytic vesicles and the recycling compartment, providing compelling evidence that integrins are normally recycled by way of endocytosis and intracellular trafficking during cell migration. This model is further refined by our demonstration that the endocytic recycling compartment reorients to retain its localization just behind the leading lamella as PMNs migrate, indicating that membrane recycling during neutrophil migration has directionality.

scholarly journals Analytical solution of Volterra's population model

2010 ◽  
Vol 22 (4) ◽  
pp. 247-250 ◽  
Author(s):  
Syed Tauseef Mohyud-Din ◽  
Ahmet Yıldırım ◽  
Yağmur Gülkanat
Keyword(s):  
Analytical Solution ◽  
Population Model

scholarly journals 2P123 Relationship between actin-activated ATPase activity and motility of Myosin Va.(Molecular motors,Poster Presentations)

2007 ◽  
Vol 47 (supplement) ◽  
pp. S143
Author(s):  
Atsuko H. Iwane ◽  
Masatoshi Nishikawa ◽  
Tomotaka Komori ◽  
Takako Mimuro ◽  
Takayuki Ariga ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Molecular Motors ◽  
Myosin Va ◽  
Poster Presentations
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