Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney

1998 ◽  
Vol 78 (4) ◽  
pp. 1109-1129 ◽  
Author(s):  
SARAH F. HAMM-ALVAREZ ◽  
MICHAEL P. SHEETZ
Keyword(s):  
Membrane Trafficking ◽  
Plasma Membranes ◽  
Motor Proteins ◽  
Cytoplasmic Dynein ◽  
Vesicle Transport ◽  
Directed Movement ◽  
Liver And Kidney ◽  
Transport Modulation ◽  
In Cells

Hamm-Alvarez, Sarah F., and Michael P. Sheetz. Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney. Physiol. Rev. 78: 1109–1129, 1998. — Microtubule-based vesicle transport driven by kinesin and cytoplasmic dynein motor proteins facilitates several membrane-trafficking steps including elements of endocytosis and exocytosis in many different cell types. Most early studies on the role of microtubule-dependent vesicle transport in membrane trafficking focused either on neurons or on simple cell lines. More recently, other work has considered the role of microtubule-based vesicle transport in other physiological systems, including kidney and liver. Investigation of the role of microtubule-based vesicle transport in membrane trafficking in cells of the kidney and liver suggests a major role for microtubule-based vesicle transport in the rapid and directed movement of ion channels and transporters to and from the apical plasma membranes, events essential for kidney and liver function and homeostasis. This review discusses the evidence supporting a role for microtubule-based vesicle transport and the motor proteins, kinesin and cytoplasmic dynein, in different aspects of membrane trafficking in cells of the kidney and liver, with emphasis on those functions such as maintenance of ion channel and transporter composition in apical membranes that are specialized functions of these organs. Evidence that defects in microtubule-based transport contribute to diseases of the kidney and liver is also discussed.

scholarly journals Dynein Light Chain 1 Regulates Dynamin-mediated F-Actin Assembly during Sperm Individualization in Drosophila

2005 ◽  
Vol 16 (7) ◽  
pp. 3107-3116 ◽  
Author(s):  
Anindya Ghosh-Roy ◽  
Bela S. Desai ◽  
Krishanu Ray
Keyword(s):  
Light Chain ◽  
Cytoplasmic Dynein ◽  
Actin Dynamics ◽  
Dynein Light Chain ◽  
Actin Assembly ◽  
Cellular Functions ◽  
Directed Movement ◽  
Cellular Processes ◽  
Dynactin Complex

Toward the end of spermiogenesis, spermatid nuclei are compacted and the clonally related spermatids individualize to become mature and active sperm. Studies in Drosophila showed that caudal end-directed movement of a microfilament-rich structure, called investment cone, expels the cytoplasmic contents of individual spermatids. F-actin dynamics plays an important role in this process. Here we report that the dynein light chain 1 (DLC1) of Drosophila is involved in two separate cellular processes during sperm individualization. It is enriched around spermatid nuclei during postelongation stages and plays an important role in the dynein-dynactin–dependent rostral retention of the nuclei during this period. In addition, DDLC1 colocalizes with dynamin along investment cones and regulates F-actin assembly at this organelle by retaining dynamin along the cones. Interestingly, we found that this process does not require the other subunits of cytoplasmic dynein-dynactin complex. Altogether, these observations suggest that DLC1 could independently regulate multiple cellular functions and established a novel role of this protein in F-actin assembly in Drosophila.

scholarly journals Cytoplasmic Dynein Nucleates Microtubules to Organize Them into Radial Arrays In Vivo

2004 ◽  
Vol 15 (6) ◽  
pp. 2742-2749 ◽  
Author(s):  
Viacheslav Malikov ◽  
Anna Kashina ◽  
Vladimir Rodionov
Keyword(s):  
Cytoplasmic Dynein ◽  
Exact Function ◽  
Necessary And Sufficient ◽  
Stimulation Of ◽  
In Cells

Numerous evidence demonstrates that dynein is crucial for organization of microtubules (MTs) into radial arrays, but its exact function in this process is unclear. Here, we studied the role of cytoplasmic dynein in MT radial array formation in the absence of the centrosome. We found that dynein is a potent MT nucleator in vitro and that stimulation of dynein activity in cytoplasmic fragments of melanophores induces nucleation-dependent formation of MT radial array in the absence of the centrosome. This new property of dynein, in combination with its known role as an MT motor that is essential for MT array organization in the absence and presence of the centrosome, makes it a unique molecule whose activity is necessary and sufficient for the formation and maintenance of MT radial arrays in cells.

scholarly journals Interaction of the Rabies Virus P Protein with the LC8 Dynein Light Chain

2000 ◽  
Vol 74 (21) ◽  
pp. 10212-10216 ◽  
Author(s):  
Hélène Raux ◽  
Anne Flamand ◽  
Danielle Blondel
Keyword(s):  
Rabies Virus ◽  
Light Chain ◽  
Cytoplasmic Dynein ◽  
Dynein Light Chain ◽  
Directed Movement ◽  
Virus Particles ◽  
P Protein ◽  
Infected Cells ◽  
Transcription And Replication

ABSTRACT The rabies virus P protein is involved in viral transcription and replication but its precise function is not clear. We investigated the role of P (CVS strain) by searching for cellular partners by using a two-hybrid screening of a PC12 cDNA library. We isolated a cDNA encoding a 10-kDa dynein light chain (LC8). LC8 is a component of cytoplasmic dynein involved in the minus end-directed movement of organelles along microtubules. We confirmed that this molecule interacts with P by coimmunoprecipitation in infected cells and in cells transfected with a plasmid encoding P protein. LC8 was also detected in virus particles. Series of deletions from the N- and C-terminal ends of P protein were used to map the LC8-binding domain to the central part of P (residues 138 to 172). These results are relevant to speculate that dynein may be involved in the axonal transport of rabies virus along microtubules through neuron cells.

scholarly journals Protein phosphatase 2C is responsible for VP-induced dephosphorylation of AQP2 serine 261

2017 ◽  
Vol 313 (2) ◽  
pp. F404-F413 ◽  
Author(s):  
Pui W. Cheung ◽  
Lars Ueberdiek ◽  
Jack Day ◽  
Richard Bouley ◽  
Dennis Brown
Keyword(s):  
Okadaic Acid ◽  
Membrane Trafficking ◽  
Protein Phosphatase ◽  
Specific Protein ◽  
Phosphatase Inhibitors ◽  
Phosphorylation State ◽  
Cellular Events ◽  
Erk Activity ◽  
In Cells

Aquaporin 2 (AQP2) trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 COOH terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in phosphorylation of serine 256 (S256), S264, and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Sanguinarine, a specific protein phosphatase (PP) 2C inhibitor, but not inhibitors of PP1, PP2A (okadaic acid), or PP2B (cyclosporine), abolished VP-induced S261 dephosphorylation. However, sanguinarine and VP significantly increased phosphorylation of ERK, a kinase that can phosphorylate S261; inhibition of ERK by PD98059 partially decreased baseline S261 phosphorylation. These data support a role of ERK in S261 phosphorylation but suggest that, upon VP treatment, increased phosphatase activity overcomes the increase in ERK activity, resulting in overall dephosphorylation of S261. We also found that sanguinarine abolished VP-induced S261 dephosphorylation in cells expressing mutated AQP2 S256A, suggesting that the phosphorylation state of S261 is independent of S256. Sanguinarine alone did not induce AQP2 membrane trafficking, nor did it inhibit VP-induced AQP2 membrane accumulation in cells and kidney tissues, suggesting that S261 does not play an observable role in acute AQP2 membrane accumulation. In conclusion, PP2C activity is required for S261 AQP2 dephosphorylation upon VP stimulation, which occurs independently of S256 phosphorylation. Understanding the pathways involved in modulating PP2C will help elucidate the role of S261 in cellular events involving AQP2.

scholarly journals Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C

2019 ◽  
Vol 218 (9) ◽  
pp. 2982-3001 ◽  
Author(s):  
Agnieszka A. Kendrick ◽  
Andrea M. Dickey ◽  
William B. Redwine ◽  
Phuoc Tien Tran ◽  
Laura Pontano Vaites ◽  
...  
Keyword(s):  
Cytoplasmic Dynein ◽  
Opposite Polarity ◽  
Full Length ◽  
Cell Periphery ◽  
Long Distance ◽  
Short Region ◽  
Cargo Transport ◽  
In Cells

The unidirectional and opposite-polarity microtubule-based motors, dynein and kinesin, drive long-distance intracellular cargo transport. Cellular observations suggest that opposite-polarity motors may be coupled. We recently identified an interaction between the cytoplasmic dynein-1 activating adaptor Hook3 and the kinesin-3 KIF1C. Here, using in vitro reconstitutions with purified components, we show that KIF1C and dynein/dynactin can exist in a complex scaffolded by Hook3. Full-length Hook3 binds to and activates dynein/dynactin motility. Hook3 also binds to a short region in the “tail” of KIF1C, but unlike dynein/dynactin, this interaction does not activate KIF1C. Hook3 scaffolding allows dynein to transport KIF1C toward the microtubule minus end, and KIF1C to transport dynein toward the microtubule plus end. In cells, KIF1C can recruit Hook3 to the cell periphery, although the cellular role of the complex containing both motors remains unknown. We propose that Hook3’s ability to scaffold dynein/dynactin and KIF1C may regulate bidirectional motility, promote motor recycling, or sequester the pool of available dynein/dynactin activating adaptors.

scholarly journals Vesicle transport along microtubular ribbons and isolation of cytoplasmic dynein from Paramecium.

1990 ◽  
Vol 111 (6) ◽  
pp. 2553-2562 ◽  
Author(s):  
C C Schroeder ◽  
A K Fok ◽  
R D Allen
Keyword(s):  
Sedimentation Coefficient ◽  
Cytoplasmic Dynein ◽  
Bovine Brain ◽  
Vesicle Transport ◽  
Relative Molecular Mass ◽  
Cytoplasmic Microtubule ◽  
Directed Movement ◽  
Brain Microtubules

Cytoplasmic microtubule-based motility in Paramecium was investigated using video-enhanced contrast microscopy, the quick-freeze, deep-etch technique, and biochemical isolations. Three distinct vesicle populations were found to be transported unidirectionally along the cytopharyngeal microtubular ribbons. This minus-end-directed movement exhibited unique in vivo features in that the vesicle transport was nonsaltatory, rapid, and predominantly along one side of the microtubular ribbons. To identify candidate motor proteins which may participate in vesicle transport, we prepared cytosolic extracts of Paramecium and used bovine brain microtubules as an affinity matrix. These preparations were found to contain a microtubule-stimulated ATPase which supported microtubule gliding in vitro. This protein was verified as a cytoplasmic dynein based upon its relative molecular mass, sedimentation coefficient of 16S, susceptibility to vanadate photocleavage, elevated CTPase/ATPase ratio, and its typical two-headed dynein morphology. This dynein was directly compared with the axonemal dyneins from Paramecium and found to differ by five criteria: morphology, sedimentation coefficient, CTPase/ATPase ratio, vanadate cleavage patterns, and polypeptide composition. The cytoplasmic dynein is therefore not an axonemal dynein precursor, but rather it represents a candidate for supporting the microtubule-based vesicle transport which proceeds along the microtubular ribbons.

scholarly journals The role of motor proteins in endosomal sorting

2011 ◽  
Vol 39 (5) ◽  
pp. 1179-1184 ◽  
Author(s):  
Sylvie D. Hunt ◽  
David J. Stephens
Keyword(s):  
Membrane Trafficking ◽  
Spatial Organization ◽  
Motor Proteins ◽  
Cytoplasmic Dynein ◽  
Endosomal Sorting ◽  
Microtubule Motors ◽  
Complex Motor ◽  
Microtubule Motor ◽  
Endosomal System ◽  
And Control

Microtubule motor proteins play key roles in the spatial organization of intracellular organelles as well as the transfer of material between them. This is well illustrated both by the vectorial transfer of biosynthetic cargo from the endoplasmic reticulum to the Golgi apparatus as well as the sorting of secretory and endocytic cargo in the endosomal system. Roles have been described for dynein and kinesin motors in each of these steps. Cytoplasmic dynein is a highly complex motor comprising multiple subunits that provide functional specialization. The family of human kinesins includes over 40 members. This complexity provides immense functional diversity, yet little is known of the specific requirements and functions of individual motors during discrete membrane trafficking steps. In the present paper, we describe some of the latest findings in this area that seek to define the mechanisms of recruitment and control of activity of microtubule motors in spatial organization and cargo trafficking through the endosomal network.

scholarly journals Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration

2021 ◽  
Vol 22 (9) ◽  
pp. 4425
Author(s):  
Alazne Arrazola Arrazola Sastre ◽  
Miriam Luque Luque Montoro ◽  
Hadriano M. Lacerda ◽  
Francisco Llavero ◽  
José L. Zugaza
Keyword(s):  
Membrane Trafficking ◽  
Neurodegenerative Disorders ◽  
Synaptic Vesicles ◽  
Intracellular Trafficking ◽  
Small Gtpases ◽  
Constant Flow ◽  
Parkinson’S Diseases ◽  
The Central Nervous System ◽  
Arf Gtpases

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration.

scholarly journals The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett
Keyword(s):  
Insulin Receptor ◽  
Plasma Clearance ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Initial Plasma ◽  
Liver And Kidney ◽  
Pre Treatment ◽  
Initial Clearance

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.

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