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The Journal of Clinical Investigation Jun 2023Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of... (Review)
Review
Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration. Here, we provide an overview of mechanisms for regulation of axonal transport; discuss how these mechanisms are disrupted in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease; and discuss therapeutic approaches targeting axonal transport.
Topics: Humans; Axonal Transport; Neurodegenerative Diseases; Neurons; Alzheimer Disease; Parkinson Disease
PubMed: 37259916
DOI: 10.1172/JCI168554 -
Current Opinion in Plant Biology Oct 2015Cytoplasmic streaming occurs widely in plants ranging from algae to angiosperms. However, the molecular mechanism and physiological role of cytoplasmic streaming have... (Review)
Review
Cytoplasmic streaming occurs widely in plants ranging from algae to angiosperms. However, the molecular mechanism and physiological role of cytoplasmic streaming have long remained unelucidated. Recent molecular genetic approaches have identified specific myosin members (XI-2 and XI-K as major and XI-1, XI-B, and XI-I as minor motive forces) for the generation of cytoplasmic streaming among 13 myosin XIs in Arabidopsis thaliana. Simultaneous knockout of these myosin XI members led to a reduced velocity of cytoplasmic streaming and marked defects of plant development. Furthermore, the artificial modifications of myosin XI-2 velocity changed plant and cell sizes along with the velocity of cytoplasmic streaming. Therefore, we assume that cytoplasmic streaming is one of the key regulators in determining plant size.
Topics: Cytoplasmic Streaming; Myosins; Plant Physiological Phenomena; Plant Proteins
PubMed: 26202096
DOI: 10.1016/j.pbi.2015.06.017 -
Journal of Cell Science Mar 2023Cells are the smallest building blocks of all living eukaryotic organisms, usually ranging from a couple of micrometers (for example, platelets) to hundreds of... (Review)
Review
Cells are the smallest building blocks of all living eukaryotic organisms, usually ranging from a couple of micrometers (for example, platelets) to hundreds of micrometers (for example, neurons and oocytes) in size. In eukaryotic cells that are more than 100 µm in diameter, very often a self-organized large-scale movement of cytoplasmic contents, known as cytoplasmic streaming, occurs to compensate for the physical constraints of large cells. In this Review, we discuss cytoplasmic streaming in multiple cell types and the mechanisms driving this event. We particularly focus on the molecular motors responsible for cytoplasmic movements and the biological roles of cytoplasmic streaming in cells. Finally, we describe bulk intercellular flow that transports cytoplasmic materials to the oocyte from its sister germline cells to drive rapid oocyte growth.
Topics: Biological Transport; Cytoplasmic Streaming; Drosophila Proteins; Dyneins; Kinesins; Microtubules; Oogenesis
PubMed: 36250267
DOI: 10.1242/jcs.260300 -
Current Opinion in Neurobiology Aug 2020Slow axonal transport conveys cytosolic and cytoskeletal proteins into axons and synapses at overall velocities that are several orders of magnitude slower than the fast... (Review)
Review
Slow axonal transport conveys cytosolic and cytoskeletal proteins into axons and synapses at overall velocities that are several orders of magnitude slower than the fast transport of membranous organelles such as vesicles and mitochondria. The phenomenon of slow transport was characterized by in vivo pulse-chase radiolabeling studies done decades ago, and proposed models emphasized an orderly cargo-movement, with apparent cohesive transport of multiple proteins and subcellular structures along axons over weeks to months. However, visualization of cytosolic and cytoskeletal cargoes in cultured neurons at much higher temporal and spatial resolution has revealed an unexpected diversity in movement - ranging from a diffusion-like biased motion, to intermittent cargo dynamics and unusual polymerization-based transport paradigms. This review provides an updated view of slow axonal transport and explores emergent mechanistic themes in this enigmatic rate-class.
Topics: Axonal Transport; Axons; Cytoskeletal Proteins; Cytoskeleton; Neurons
PubMed: 32361600
DOI: 10.1016/j.conb.2020.03.015 -
Cold Spring Harbor Perspectives in... Mar 2018The delivery of intracellular material within cells is crucial for maintaining normal function. Myosins transport a wide variety of cargo, ranging from vesicles to... (Review)
Review
The delivery of intracellular material within cells is crucial for maintaining normal function. Myosins transport a wide variety of cargo, ranging from vesicles to ribonuclear protein particles (RNPs), in plants, fungi, and metazoa. The properties of a given myosin transporter are adapted to move on different actin filament tracks, either on the disordered actin networks at the cell cortex or along highly organized actin bundles to distribute their cargo in a localized manner or move it across long distances in the cell. Transport is controlled by selective recruitment of the myosin to its cargo that also plays a role in activation of the motor.
Topics: Animals; Biological Transport; Cytoplasmic Streaming; Humans; Myosins; Organelles; Plants; RNA; Ribonucleoproteins; Secretory Vesicles; Transport Vesicles
PubMed: 29496823
DOI: 10.1101/cshperspect.a021972 -
Biochemical and Biophysical Research... Nov 2018Actin is one of the three major cytoskeletal components in eukaryotic cells. Myosin XI is an actin-based motor protein in plant cells. Organelles are attached to myosin... (Review)
Review
Actin is one of the three major cytoskeletal components in eukaryotic cells. Myosin XI is an actin-based motor protein in plant cells. Organelles are attached to myosin XI and translocated along the actin filaments. This dynamic actin-myosin XI system plays a major role in subcellular organelle transport and cytoplasmic streaming. Previous studies have revealed that myosin-driven transport and the actin cytoskeleton play essential roles in plant cell growth. Recent data have indicated that the actin-myosin XI cytoskeleton is essential for not only cell growth but also reproductive processes and responses to the environment. In this review, we have summarized previous reports regarding the role of the actin-myosin XI cytoskeleton in cytoplasmic streaming and plant development and recent advances in the understanding of the functions of actin-myosin XI cytoskeleton in Arabidopsis thaliana.
Topics: Actin Cytoskeleton; Actins; Arabidopsis; Arabidopsis Proteins; Biomechanical Phenomena; Cytoplasmic Streaming; Gene Expression Regulation, Developmental; Gene Expression Regulation, Plant; Myosins; Organ Specificity; Plant Cells; Plant Leaves; Plant Roots; Plant Stems; Protein Isoforms; Reproduction
PubMed: 29307817
DOI: 10.1016/j.bbrc.2017.12.169 -
International Journal of Molecular... Apr 2022Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs) and leads to progressive vision loss. The first pathological signs can be seen at... (Review)
Review
Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs) and leads to progressive vision loss. The first pathological signs can be seen at the optic nerve head (ONH), the structure where RGC axons leave the retina to compose the optic nerve. Besides damage of the axonal cytoskeleton, axonal transport deficits at the ONH have been described as an important feature of glaucoma. Axonal transport is essential for proper neuronal function, including transport of organelles, synaptic components, vesicles, and neurotrophic factors. Impairment of axonal transport has been related to several neurodegenerative conditions. Studies on axonal transport in glaucoma include analysis in different animal models and in humans, and indicate that its failure happens mainly in the ONH and early in disease progression, preceding axonal and somal degeneration. Thus, a better understanding of the role of axonal transport in glaucoma is not only pivotal to decipher disease mechanisms but could also enable early therapies that might prevent irreversible neuronal damage at an early time point. In this review we present the current evidence of axonal transport impairment in glaucomatous neurodegeneration and summarize the methods employed to evaluate transport in this disease.
Topics: Animals; Axonal Transport; Axons; Disease Models, Animal; Glaucoma; Neurodegenerative Diseases; Retinal Ganglion Cells
PubMed: 35409291
DOI: 10.3390/ijms23073935 -
Cell Structure and Function Jul 1984
Review
Topics: Actins; Cell Membrane; Cytoplasm; Models, Biological; Movement; Myosins; Plants
PubMed: 6383637
DOI: No ID Found -
Current Opinion in Neurobiology Aug 2018Lysosomes perform degradative functions that are important for all cells. However, neurons are particularly dependent on optimal lysosome function due to their extremes... (Review)
Review
Lysosomes perform degradative functions that are important for all cells. However, neurons are particularly dependent on optimal lysosome function due to their extremes of longevity, size and polarity. Axons in particular exemplify the major spatial challenges faced by neurons in the maintenance of lysosome biogenesis and function. What impact does this have on the regulation and functions of lysosomes in axons? This review focuses on the mechanisms whereby axonal lysosome biogenesis, transport and function are adapted to meet neuronal demand. Important features include the dynamic relationship between endosomes, autophagosomes and lysosomes as well as the transport mechanisms that support the movement of lysosome precursors in axons. A picture is emerging wherein intermediates in the lysosome maturation processes that would only exist transiently within the crowded confines of a neuronal cell body are spatially and temporally separated over the extreme distances encountered in axons. Axons may thus offer significant opportunities for the analysis of the mechanisms that control lysosome biogenesis. Insights from the genetics and pathology of human neurodegenerative diseases furthermore emphasize the importance of efficient axonal transport of lysosomes and their precursors.
Topics: Animals; Axonal Transport; Humans; Lysosomes; Neurons
PubMed: 29529416
DOI: 10.1016/j.conb.2018.02.020 -
Frontiers in Endocrinology 2023Diabetic peripheral neuropathy (DPN) is a chronic and prevalent metabolic disease that gravely endangers human health and seriously affects the quality of life of... (Review)
Review
Diabetic peripheral neuropathy (DPN) is a chronic and prevalent metabolic disease that gravely endangers human health and seriously affects the quality of life of hyperglycemic patients. More seriously, it can lead to amputation and neuropathic pain, imposing a severe financial burden on patients and the healthcare system. Even with strict glycemic control or pancreas transplantation, peripheral nerve damage is difficult to reverse. Most current treatment options for DPN can only treat the symptoms but not the underlying mechanism. Patients with long-term diabetes mellitus (DM) develop axonal transport dysfunction, which could be an important factor in causing or exacerbating DPN. This review explores the underlying mechanisms that may be related to axonal transport impairment and cytoskeletal changes caused by DM, and the relevance of the latter with the occurrence and progression of DPN, including nerve fiber loss, diminished nerve conduction velocity, and impaired nerve regeneration, and also predicts possible therapeutic strategies. Understanding the mechanisms of diabetic neuronal injury is essential to prevent the deterioration of DPN and to develop new therapeutic strategies. Timely and effective improvement of axonal transport impairment is particularly critical for the treatment of peripheral neuropathies.
Topics: Humans; Diabetic Neuropathies; Axonal Transport; Quality of Life; Neuralgia; Pancreas Transplantation; Diabetes Mellitus
PubMed: 37056668
DOI: 10.3389/fendo.2023.1136796