scholarly journals Recruitment of dynein to late endosomes and lysosomes through light intermediate chains

2011 ◽  
Vol 22 (4) ◽  
pp. 467-477 ◽  
Author(s):  
Serena C. Tan ◽  
Julian Scherer ◽  
Richard B. Vallee
Keyword(s):  
Full Range ◽  
Cytoplasmic Dynein ◽  
Endocytic Pathway ◽  
Cellular Processes ◽  
Late Endosomes ◽  
Wide Range ◽  
Range Of Functions ◽  
Specific Association ◽  
Dynein Light Intermediate Chains ◽  
Intermediate Chains

Cytoplasmic dynein is involved in a wide range of cellular processes, but how it is regulated and how it recognizes an extremely wide range of cargo are incompletely understood. The dynein light intermediate chains, LIC1 and LIC2 (DYNC1LI1 and DYNC1LI2, respectively), have been implicated in cargo binding, but their full range of functions is unknown. Using LIC isoform-specific antibodies, we report the first characterization of their subcellular distribution and identify a specific association with elements of the late endocytic pathway, but not other vesicular compartments. LIC1 and LIC2 RNA interference (RNAi) each specifically disrupts the distribution of lysosomes and late endosomes. Stimulation of dynein-mediated late-endosomal transport by the Rab7-interacting lysosomal protein (RILP) is reversed by LIC1 RNAi, which displaces dynein, but not dynactin, from these structures. Conversely, expression of ΔN-RILP or the dynactin subunit dynamitin each fails to displace dynein, but not dynactin. Thus, using a variety of complementary approaches, our results indicate a novel specific role for the LICs in dynein recruitment to components of the late endocytic pathway.

Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

2011 ◽  
Vol 439 (3) ◽  
pp. 349-378 ◽  
Author(s):  
Anthony J. Morgan ◽  
Frances M. Platt ◽  
Emyr Lloyd-Evans ◽  
Antony Galione
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Late Endosomes ◽  
Wide Range ◽  
Health And Disease ◽  
Lysosome Related Organelles ◽  
Cellular Compartments ◽  
Endosomal Vesicles ◽  
Intracellular Targets

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

scholarly journals LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains

Open Biology ◽  
2018 ◽  
Vol 8 (6) ◽  
pp. 170202 ◽  
Author(s):  
Sirong Ou ◽  
Mei-Hua Tan ◽  
Ting Weng ◽  
HoiYeung Li ◽  
Cheng-Gee Koh
Keyword(s):  
Protein Transport ◽  
Protein Localization ◽  
Cytoplasmic Dynein ◽  
Spindle Pole ◽  
Centrosomal Protein ◽  
And Function ◽  
Cytoskeleton Dynamics ◽  
Dynein Light Intermediate Chains ◽  
Intermediate Chains ◽  
Mitotic Spindle Pole

Abnormal centrosome number and function have been implicated in tumour development. LIM kinase1 (LIMK1), a regulator of actin cytoskeleton dynamics, is found to localize at the mitotic centrosome. However, its role at the centrosome is not fully explored. Here, we report that LIMK1 depletion resulted in multi-polar spindles and defocusing of centrosomes, implicating its involvement in the regulation of mitotic centrosome integrity. LIMK1 could influence centrosome integrity by modulating centrosomal protein localization at the spindle pole. Interestingly, dynein light intermediate chains (LICs) are able to rescue the defects observed in LIMK1-depleted cells. We found that LICs are potential novel interacting partners and substrates of LIMK1 and that LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity.

scholarly journals The RhoGEF Trio: A Protein with a Wide Range of Functions in the Vascular Endothelium

2021 ◽  
Vol 22 (18) ◽  
pp. 10168
Author(s):  
Lanette Kempers ◽  
Amber J. M. Driessen ◽  
Jos van Rijssel ◽  
Martijn A. Nolte ◽  
Jaap D. van Buul
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Function ◽  
Small Gtpases ◽  
Nucleotide Exchange ◽  
Endothelial Cell Function ◽  
Cellular Processes ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Wide Range ◽  
Range Of Functions

Many cellular processes are controlled by small GTPases, which can be activated by guanine nucleotide exchange factors (GEFs). The RhoGEF Trio contains two GEF domains that differentially activate the small GTPases such as Rac1/RhoG and RhoA. These small RhoGTPases are mainly involved in the remodeling of the actin cytoskeleton. In the endothelium, they regulate junctional stabilization and play a crucial role in angiogenesis and endothelial barrier integrity. Multiple extracellular signals originating from different vascular processes can influence the activity of Trio and thereby the regulation of the forementioned small GTPases and actin cytoskeleton. This review elucidates how various signals regulate Trio in a distinct manner, resulting in different functional outcomes that are crucial for endothelial cell function in response to inflammation.

scholarly journals Distinct roles for dynein light intermediate chains in neurogenesis, migration, and terminal somal translocation

2019 ◽  
Vol 218 (3) ◽  
pp. 808-819 ◽  
Author(s):  
João Carlos Gonçalves ◽  
Tiago J. Dantas ◽  
Richard B. Vallee
Keyword(s):  
Neuronal Migration ◽  
Cytoplasmic Dynein ◽  
Neural Progenitors ◽  
In Utero Electroporation ◽  
Neocortical Development ◽  
Newborn Neurons ◽  
Dynein Light Intermediate Chains ◽  
Intermediate Chains ◽  
Developing Rat ◽  
Insight Into

Cytoplasmic dynein participates in multiple aspects of neocortical development. These include neural progenitor proliferation, morphogenesis, and neuronal migration. The cytoplasmic dynein light intermediate chains (LICs) 1 and 2 are cargo-binding subunits, though their relative roles are not well understood. Here, we used in utero electroporation of shRNAs or LIC functional domains to determine the relative contributions of the two LICs in the developing rat brain. We find that LIC1, through BicD2, is required for apical nuclear migration in neural progenitors. In newborn neurons, we observe specific roles for LIC1 in the multipolar to bipolar transition and glial-guided neuronal migration. In contrast, LIC2 contributes to a novel dynein role in the little-studied mode of migration, terminal somal translocation. Together, our results provide novel insight into the LICs’ unique functions during brain development and dynein regulation overall.

scholarly journals Role of the RAB7 Protein in Tumor Progression and Cisplatin Chemoresistance

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1096 ◽  
Author(s):  
Guerra ◽  
Bucci
Keyword(s):  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Endocytic Pathway ◽  
Cellular Processes ◽  
Molecular Events ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Cellular Context ◽  
Guanosine Triphosphatase

RAB7 is a small guanosine triphosphatase (GTPase) extensively studied as regulator of vesicular trafficking. Indeed, its role is fundamental in several steps of the late endocytic pathway, including endosome maturation, transport from early endosomes to late endosomes and lysosomes, clustering and fusion of late endosomes and lysosomes in the perinuclear region and lysosomal biogenesis. Besides endocytosis, RAB7 is important for a number of other cellular processes among which, autophagy, apoptosis, signaling, and cell migration. Given the importance of RAB7 in these cellular processes, the interest to study the role of RAB7 in cancer progression is widely grown. Here, we describe the current understanding of oncogenic and oncosuppressor functions of RAB7 analyzing cellular context and other environmental factors in which it elicits pro and/or antitumorigenic effects. We also discuss the role of RAB7 in cisplatin resistance associated with its ability to regulate the late endosomal pathway, lysosomal biogenesis and extracellular vesicle secretion. Finally, we examined the potential cancer therapeutic strategies targeting the different molecular events in which RAB7 is involved.

scholarly journals Lipid Droplet Motility and Organelle Contacts

Contact ◽  
2019 ◽  
Vol 2 ◽  
pp. 251525641989568 ◽  
Author(s):  
Marcus D. Kilwein ◽  
Michael A. Welte
Keyword(s):  
Actin Polymerization ◽  
Energy Homeostasis ◽  
Cytoplasmic Dynein ◽  
Regulatory Pathways ◽  
Cellular Processes ◽  
Daughter Cells ◽  
Wide Range ◽  
A Cell ◽  
Cell Type Specific ◽  
Type V

Lipid droplets (LDs) are fat storage organelles integral to energy homeostasis and a wide range of cellular processes. LDs physically and functionally interact with many partner organelles, including the endoplasmic reticulum, mitochondria, lysosomes, and peroxisomes. Recent findings suggest that the dynamics of LD interorganelle contacts is in part controlled by LD intracellular motility. LDs can be transported directly by motor proteins along either actin filaments or microtubules, via Kinesin-1, Cytoplasmic Dynein, and type V Myosins. LDs can also be propelled indirectly, by hitchhiking on other organelles, cytoplasmic flows, and potentially actin polymerization. Although the anchors that attach motors to LDs remain elusive, other regulators of LD motility have been identified, ranging from modification of the tracks to motor cofactors to members of the perilipin family of LD proteins. Manipulating these regulatory pathways provides a tool to probe whether altered motility affects organelle contacts and has revealed that LD motility can promote interactions with numerous partners, with profound consequences for metabolism. LD motility can cause dramatic redistribution of LDs between a clustered and a dispersed state, resulting in altered organelle contacts and LD turnover. We propose that LD motility can thus promote switches in the metabolic state of a cell. Finally, LD motility is also important for LD allocation during cell division. In a number of animal embryos, uneven allocation results in a large difference in LD content in distinct daughter cells, suggesting cell-type specific LD needs.

scholarly journals Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion

2014 ◽  
Vol 207 (4) ◽  
pp. 499-516 ◽  
Author(s):  
Laura A. Jones ◽  
Cécile Villemant ◽  
Toby Starborg ◽  
Anna Salter ◽  
Georgina Goddard ◽  
...  
Keyword(s):  
Cell Division ◽  
Cytoplasmic Dynein ◽  
Small Interfering Rnas ◽  
Cellular Functions ◽  
Multipolar Spindles ◽  
Early Embryos ◽  
Microtubule Motor ◽  
Morpholino Oligonucleotides ◽  
Dynein Light Intermediate Chains ◽  
Intermediate Chains

Cytoplasmic dynein 1 (dynein) is a minus end–directed microtubule motor protein with many cellular functions, including during cell division. The role of the light intermediate chains (LICs; DYNC1LI1 and 2) within the complex is poorly understood. In this paper, we have used small interfering RNAs or morpholino oligonucleotides to deplete the LICs in human cell lines and Xenopus laevis early embryos to dissect the LICs’ role in cell division. We show that although dynein lacking LICs drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. Multipolar spindles with poles that contain single centrioles were formed in cells lacking LICs, indicating that they are needed for maintaining centrosome integrity. The formation of multipolar spindles via centrosome splitting after LIC depletion could be rescued by inhibiting Eg5. This suggests a novel role for the dynein complex, counteracted by Eg5, in the maintenance of centriole cohesion during mitosis.

scholarly journals Subcellular tube guidance requires anchoring of the apical and basal actin cortices through late endosomes

2021 ◽  
Author(s):  
Luis Daniel Rios-Barrera ◽  
Maria Leptin
Keyword(s):  
Protein Trafficking ◽  
Plasma Membranes ◽  
Basal Membrane ◽  
Endocytic Pathway ◽  
Apical Plasma Membrane ◽  
Cortical Actin ◽  
Cellular Processes ◽  
Late Endosomes ◽  
Membrane Compartments ◽  
Membrane Morphogenesis

The actin cytoskeleton participates in a range of cellular processes. It supports cell shape changes by propagating forces within cells and between cells and their environment. Terminal cells of the Drosophila respiratory system form a subcellular tube by invaginating their apical plasma membrane; cortical actin networks at the basal and apical plasma membranes are critical for proper morphogenesis. Basal actin affects apical membrane morphogenesis, and it is not known how the two separate actin pools communicate. We report here that actin assembles around vesicles of the late endocytic pathway, which are present in the growth cone of the cell, between the tip of the subcellular tube and the leading filopodia of the basal membrane. Actin organized at late endosomes extends towards both membrane compartments. Preventing proper actin nucleation at late endosomes disturbs the directionality of tube growth, uncoupling it from the direction of cell elongation. Severing actin in this area affects tube integrity. These findings demonstrate a role for the late endocytic pathway in organizing actin for proper cell morphogenesis, in addition to its known role in membrane and protein trafficking.

scholarly journals Role of Dynactin in Endocytic Traffic: Effects of Dynamitin Overexpression and Colocalization with CLIP-170

1999 ◽  
Vol 10 (12) ◽  
pp. 4107-4120 ◽  
Author(s):  
Caterina Valetti ◽  
Dawn M. Wetzel ◽  
Michael Schrader ◽  
M. Josh Hasbani ◽  
Steven R. Gill ◽  
...  
Keyword(s):  
Cytoplasmic Dynein ◽  
Endocytic Pathway ◽  
Wild Type ◽  
Microtubule Binding ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Endocytic Traffic ◽  
Binding Subunit

The flow of material from peripheral, early endosomes to late endosomes requires microtubules and is thought to be facilitated by the minus end-directed motor cytoplasmic dynein and its activator dynactin. The microtubule-binding protein CLIP-170 may also play a role by providing an early link to endosomes. Here, we show that perturbation of dynactin function in vivo affects endosome dynamics and trafficking. Endosome movement, which is normally bidirectional, is completely inhibited. Receptor-mediated uptake and recycling occur normally, but cells are less susceptible to infection by enveloped viruses that require delivery to late endosomes, and they show reduced accumulation of lysosomally targeted probes. Dynactin colocalizes at microtubule plus ends with CLIP-170 in a way that depends on CLIP-170’s putative cargo-binding domain. Overexpression studies using p150Glued, the microtubule-binding subunit of dynactin, and mutant and wild-type forms of CLIP-170 indicate that CLIP-170 recruits dynactin to microtubule ends. These data suggest a new model for the formation of motile complexes of endosomes and microtubules early in the endocytic pathway.

scholarly journals Identification of 56 Proteins Involved in Embryo–Maternal Interactions in the Bovine Oviduct

2020 ◽  
Vol 21 (2) ◽  
pp. 466 ◽  
Author(s):  
Charles Banliat ◽  
Guillaume Tsikis ◽  
Valérie Labas ◽  
Ana-Paula Teixeira-Gomes ◽  
Emmanuelle Com ◽  
...  
Keyword(s):  
Protein Interactions ◽  
High Resolution Mass Spectrometry ◽  
Bovine Embryo ◽  
Interacting Proteins ◽  
Cellular Processes ◽  
Wide Range ◽  
Range Of Functions ◽  
First Time

The bovine embryo develops in contact with the oviductal fluid (OF) during the first 4–5 days of pregnancy. The aim of this study was to decipher the protein interactions occurring between the developing embryo and surrounding OF. In-vitro produced 4–6 cell and morula embryos were incubated or not (controls) in post-ovulatory OF (OF-treated embryos) and proteins were then analyzed and quantified by high resolution mass spectrometry (MS) in both embryo groups and in OF. A comparative analysis of MS data allowed the identification and quantification of 56 embryo-interacting proteins originated from the OF, including oviductin (OVGP1) and several annexins (ANXA1, ANXA2, ANXA4) as the most abundant ones. Some embryo-interacting proteins were developmental stage-specific, showing a modulating role of the embryo in protein interactions. Three interacting proteins (OVGP1, ANXA1 and PYGL) were immunolocalized in the perivitelline space and in blastomeres, showing that OF proteins were able to cross the zona pellucida and be taken up by the embryo. Interacting proteins were involved in a wide range of functions, among which metabolism and cellular processes were predominant. This study identified for the first time a high number of oviductal embryo-interacting proteins, paving the way for further targeted studies of proteins potentially involved in the establishment of pregnancy in cattle.

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