scholarly journals Trk Activation of the ERK1/2 Kinase Pathway Stimulates Intermediate Chain Phosphorylation and Recruits Cytoplasmic Dynein to Signaling Endosomes for Retrograde Axonal Transport

2012 ◽  
Vol 32 (44) ◽  
pp. 15495-15510 ◽  
Author(s):  
D. J. Mitchell ◽  
K. R. Blasier ◽  
E. D. Jeffery ◽  
M. W. Ross ◽  
A. K. Pullikuth ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Kinase Pathway ◽  
Intermediate Chain

scholarly journals Identification and developmental regulation of a neuron-specific subunit of cytoplasmic dynein.

1996 ◽  
Vol 7 (2) ◽  
pp. 331-343 ◽  
Author(s):  
K K Pfister ◽  
M W Salata ◽  
J F Dillman ◽  
E Torre ◽  
R J Lye
Keyword(s):  
Axonal Transport ◽  
Developmental Regulation ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Protein Isoforms ◽  
Cultured Neurons ◽  
Developmentally Regulated ◽  
Time Period ◽  
Intermediate Chains

Cytoplasmic dynein is the microtubule minus-end-directed motor for the retrograde axonal transport of membranous organelles. Because of its similarity to the intermediate chains of flagellar dynein, the 74-kDa intermediate chain (IC74) subunit of dynein is thought to be involved in binding dynein to its membranous organelle cargo. Previously, we identified six isoforms of the IC74 cytoplasmic dynein subunit in the brain. We further demonstrated that cultured glia and neurons expressed different dynein IC74 isoforms and phospho-isoforms. Two isoforms were observed when dynein from glia was analyzed. When dynein from cultured neurons was analyzed, six IC74 isoforms were observed, although the relative amounts of the dynein isoforms from cultured neurons differed from those found in dynein from brain. To better understand the role of the neuronal IC74 isoforms and identify neuron-specific IC74 dynein subunits, the expression of the IC74 protein isoforms and mRNAs of various tissues were compared. As a result of this comparison, the identity of each of the isoform spots observed on two-dimensional gels was correlated with the products of each of the IC74 mRNAs. We also found that between the fifteenth day of gestation (E15) and the fifth day after birth (P5), the relative expression of the IC74 protein isoforms changes, demonstrating that the expression of IC74 isoforms is developmentally regulated in brain. During this time period, there is relatively little change in the abundance of the various IC74 mRNAs. The E15 to P5 time period is one of rapid process extension and initial pattern formation in the rat brain. This result indicates that the changes in neuronal IC74 isoforms coincide with neuronal differentiation, in particular the extension of processes. This suggests a role for the neuronal IC74 isoforms in the establishment or regulation of retrograde axonal transport.

scholarly journals A Conserved Role for Vezatin Proteins in Cargo-Specific Regulation of Retrograde Axonal Transport

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 431-445 ◽  
Author(s):  
Michael A. Spinner ◽  
Katherine Pinter ◽  
Catherine M. Drerup ◽  
Tory G. Herman
Keyword(s):  
Axonal Transport ◽  
Retrograde Transport ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Cell Junctions ◽  
Loss Of Function ◽  
Axon Terminals ◽  
Bmp Receptors ◽  
New Material ◽  
Specific Regulation

Active transport of organelles within axons is critical for neuronal health. Retrograde axonal transport, in particular, relays neurotrophic signals received by axon terminals to the nucleus and circulates new material among en passant synapses. A single motor protein complex, cytoplasmic dynein, is responsible for nearly all retrograde transport within axons: its linkage to and transport of diverse cargos is achieved by cargo-specific regulators. Here, we identify Vezatin as a conserved regulator of retrograde axonal transport. Vertebrate Vezatin (Vezt) is required for the maturation and maintenance of cell-cell junctions and has not previously been implicated in axonal transport. However, a related fungal protein, VezA, has been shown to regulate retrograde transport of endosomes in hyphae. In a forward genetic screen, we identified a loss-of-function mutation in the Drosophila vezatin-like (vezl) gene. We here show that vezl loss prevents a subset of endosomes, including signaling endosomes containing activated BMP receptors, from initiating transport out of motor neuron terminal boutons. vezl loss also decreases the transport of endosomes and dense core vesicles, but not mitochondria, within axon shafts. We disrupted vezt in zebrafish and found that vezt loss specifically impairs the retrograde axonal transport of late endosomes, causing their accumulation in axon terminals. Our work establishes a conserved, cargo-specific role for Vezatin proteins in retrograde axonal transport.

scholarly journals Role of Dynein and Dynactin (DCTN-1) in Neurodegenerative Diseases

2019 ◽  
pp. 53-58
Author(s):  
Rajib Dutta ◽  
Swatilekha Roy Sarkar
Keyword(s):  
Neurodegenerative Diseases ◽  
Axonal Transport ◽  
Molecular Motor ◽  
Neuronal Cell ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Motor Neuropathy ◽  
Excitatory Neurotransmitter ◽  
Charcot Marie Tooth Disease

The pathophysiology and concept of degeneration in central nervous system is very complex and overwhelming at times. There is a complex mechanism which exists among different molecules in the cytoplasm of cell bodies of neurons, antegrade and retrograde axonal transport of cargoes and accumulation of certain substances and proteins which can influence the excitatory neurotransmitter like glutamate initiating the process of neurodegeneration. Neurons have extensive processes and communication between those processes and the cell body is crucial to neuronal function, viability and survival over time with progression of age. Researchers believe neurons are uniquely dependent on microtubule-based cargo transport. There is enough evidence to support that deficits in retrograde axonal transport contribute to pathogenesis in multiple neurodegenerative diseases. Cytoplasmic dynein and its regulation by Dynactin (DCTN1) is the major molecular motor cargo involved in autophagy, mitosis and neuronal cell survival. Mutation in dynactin gene located in 2p13.1,is indeed studied very extensively and is considered to be involved directly or indirectly to various conditions like Perry syndrome, familial and sporadic Amyotrophic lateral sclerosis, Hereditary spastic paraplegia, Spinocerebellar Ataxia (SCA-5), Huntingtons disease, Alzheimers disease, Charcot marie tooth disease, Hereditary motor neuropathy 7B, prion disease, parkinsons disease, malformation of cortical development, polymicrogyria to name a few with exception of Multiple Sclerosis (MS).

scholarly journals Vezatin is required for the retrograde axonal transport of endosomes in Drosophila and zebrafish

2020 ◽  
Author(s):  
Michael A. Spinner ◽  
Katherine Pinter ◽  
Catherine M. Drerup ◽  
Tory G. Herman
Keyword(s):  
Motor Neuron ◽  
Axonal Transport ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Loss Of Function ◽  
Axon Terminals ◽  
Bmp Receptors ◽  
Late Endosomes ◽  
Transport Loss ◽  
New Material

ABSTRACTActive transport of organelles within axons is critical for neuronal health. Retrograde axonal transport, in particular, relays neurotrophic signals received by axon terminals to the nucleus and circulates new material among en passant synapses. The single retrograde motor, cytoplasmic dynein, is linked to diverse cargos by adaptors that promote dynein motility. Here we identify Vezatin as a new, cargo-specific regulator of retrograde axonal transport. Loss-of-function mutations in the Drosophila vezatin-like (vezl) gene prevent signaling endosomes containing activated BMP receptors from initiating transport out of motor neuron terminal boutons. vezl loss also decreases the transport of endosomes and dense core vesicles (DCVs) within axon shafts. While vertebrate Vezatin (Vezt) has not previously been implicated in axonal transport, we show that vezt loss in zebrafish impairs the retrograde movement of late endosomes, causing their accumulation in axon terminals. Our work establishes a new, conserved, cargo-specific role for Vezatin proteins in axonal transport.

Retrograde Axonal Transport: Applications in Tmphic Factor Research

2003 ◽  
pp. 247-290 ◽  
Author(s):  
Vkssilis E. Koliatsos ◽  
Donald L. Price
Keyword(s):  
Axonal Transport ◽  
Retrograde Axonal Transport
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