scholarly journals A role for Dynlt3 in melanosome movement, distribution, acidity and transfer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Zackie Aktary ◽  
Alejandro Conde-Perez ◽  
Florian Rambow ◽  
Mathilde Di Marco ◽  
François Amblard ◽  
...  
Keyword(s):  
Mus Musculus ◽  
Skin Pigmentation ◽  
Stage Iv ◽  
Cytoplasmic Dynein ◽  
Signalling Pathway ◽  
Cell Stage ◽  
Cellular Processes ◽  
Space And Time ◽  
Peripheral Location ◽  
Directional Motion

AbstractSkin pigmentation is dependent on cellular processes including melanosome biogenesis, transport, maturation and transfer to keratinocytes. However, how the cells finely control these processes in space and time to ensure proper pigmentation remains unclear. Here, we show that a component of the cytoplasmic dynein complex, Dynlt3, is required for efficient melanosome transport, acidity and transfer. In Mus musculus melanocytes with decreased levels of Dynlt3, pigmented melanosomes undergo a more directional motion, leading to their peripheral location in the cell. Stage IV melanosomes are more acidic, but still heavily pigmented, resulting in a less efficient melanosome transfer. Finally, the level of Dynlt3 is dependent on β-catenin activity, revealing a function of the Wnt/β-catenin signalling pathway during melanocyte and skin pigmentation, by coupling the transport, positioning and acidity of melanosomes required for their transfer.

scholarly journals Dynlt3, a novel fundamental regulator of melanosome movement, distribution, maturation and transfer

2021 ◽  
Author(s):  
Zackie Aktary ◽  
Alejandro Conde-Perez ◽  
Florian Rambow ◽  
Mathilde Di Marco ◽  
François Amblard ◽  
...  
Keyword(s):  
Skin Pigmentation ◽  
Stage Iv ◽  
Convective Motion ◽  
Cytoplasmic Dynein ◽  
Signalling Pathway ◽  
Cellular Processes ◽  
Space And Time ◽  
Peripheral Location

ABSTRACTSkin pigmentation is dependent on cellular processes including melanosome biogenesis, transport, maturation and transfer to keratinocytes. However, how the cells finely control these processes in space and time to ensure proper pigmentation remains unclear. Here, we show that a component of the cytoplasmic dynein complex, Dynlt3, is required for efficient melanosome transport, maturation and transfer. In melanocytes with decreased levels of Dynlt3, pigmented melanosomes undergo a more directional (convective) motion leading to their peripheral location in the cell, and are not fully matured. Stage IV melanosomes are more acidic, but still heavily pigmented, resulting in a less efficient melanosome transfer. Finally, the level of Dynlt3 is dependent on β-catenin activity, revealing a novel function of the Wnt/β-catenin signalling pathway during melanocyte and skin pigmentation, by coupling the transport, position and maturation of melanosomes required for their transfer.

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 Spermatozoa telomeres determine telomere length in early embryos and offspring

Reproduction ◽  
2016 ◽  
Vol 151 (1) ◽  
pp. 1-7 ◽  
Author(s):  
C de Frutos ◽  
A P López-Cardona ◽  
N Fonseca Balvís ◽  
R Laguna-Barraza ◽  
D Rizos ◽  
...  
Keyword(s):  
Telomere Length ◽  
Mus Musculus ◽  
Mus Spretus ◽  
Cell Stage ◽  
Young Males ◽  
Early Embryos ◽  
Parent Of Origin ◽  
Telomere Lengthening ◽  
Zygote Stage

Offspring telomere length (TL) has been correlated with paternal TL, but the mechanism for this parent of origin-specific inheritance remains unclear. The objective of this study has been to determine the role of spermatozoa TL in embryonic telomere lengthening by using two mouse models showing dimorphism in their spermatozoa TL: Mus musculus vs Mus spretus and old vs young Mus musculus. Mus spretus spermatozoa displayed a shorter TL than Mus musculus. Hybrid offspring exhibited lower TL compared with Mus musculus starting at the two-cell stage, before the onset of telomerase expression. To analyze the role of spermatozoa telomeres in early telomere lengthening, we compared the TL in oocytes, zygotes, two-cell embryos and blastocysts produced by parthenogenesis or by fertilization with Mus musculus or Mus spretus spermatozoa. TL was significantly higher in spermatozoa compared with oocytes, and it increased significantly from the oocyte to the zygote stage in those embryos fertilized with Mus musculus spermatozoa, but not in those fertilized with Mus spretus spermatozoa or produced by parthenogenesis. A further increase was noted from the zygote to the two-cell stage in fertilized Mus musculus embryos, whereas hybrid embryos maintained the oocyte TL. Spermatozoa TL shortened with age in Mus musculus and the offspring from young males showed a significantly higher TL compared with that fathered by old males. These significant differences were already noticeable at the two-cell stage. These results suggest that spermatozoa telomeres act as a guide for telomerase-independent telomere lengthening resulting in differences in TL that persist after birth.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/151/1/1/suppl/DC1.

scholarly journals The Canonical Wnt Pathway as a Key Regulator in Liver Development, Differentiation and Homeostatic Renewal

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1163
Author(s):  
Sebastian L. Wild ◽  
Aya Elghajiji ◽  
Carmen Grimaldos Rodriguez ◽  
Stephen D. Weston ◽  
Zoë D. Burke ◽  
...  
Keyword(s):  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Signalling Pathway ◽  
Fate Specification ◽  
Cellular Processes ◽  
Recent Developments ◽  
Body Patterning ◽  
Important Regulator ◽  
Canonical Wnt

The canonical Wnt (Wnt/β-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/β-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/β-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/β-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.

Crosstalk between TGF-β1 signalling pathway and microRNAs in renal cancer

2020 ◽  
Vol 7 ◽  
pp. 1-14
Author(s):  
Joanna Bogusławska
Keyword(s):  
Renal Cancer ◽  
Potential Role ◽  
Signalling Pathway ◽  
Small Noncoding Rnas ◽  
Cellular Processes ◽  
Genes Expression ◽  
Mutual Regulation ◽  
Important Regulator ◽  
Oncogenic Function ◽  
Tgf Β1

Alterations in TGF-β1 signalling in renal cancer are accompanied by disturbed expression of microRNAs (miRNAs). TGF-β1 is an important regulator of key cellular processes and contributes to the development of many diseases, including cancer. At early cancer stages, TGF-β1 inhibits proliferation and tumour growth, while as the disease progresses, TGF-β1 stimulates metastasis. This dual TGF-β1 effect in cancers is called the “TGF-β1 paradox”. miRNAs – small, noncoding RNAs which regulate genes expression may contribute to the switching of TGF-β1 from suppressor to oncogenic function. The article presents the latest information regarding mutual regulation between miRNAs and the TGF-β1 signalling pathway as well as its potential role in the treatment of kidney cancer.

scholarly journals Sertoli cell processes have axoplasmic features: an ordered microtubule distribution and an abundant high molecular weight microtubule-associated protein (cytoplasmic dynein).

1988 ◽  
Vol 107 (5) ◽  
pp. 1767-1776 ◽  
Author(s):  
M D Neely ◽  
K Boekelheide
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Sertoli Cell ◽  
Gradient Centrifugation ◽  
Sucrose Density Gradient ◽  
Cytoplasmic Dynein ◽  
Microtubule Assembly ◽  
Sucrose Density Gradient Centrifugation ◽  
Cell Stage ◽  
Structural And Functional Properties

Microtubules in the cytoplasm of rat Sertoli cell stage VI-VIII testicular seminiferous epithelium were studied morphometrically by electron microscopy. The Sertoli cell microtubules demonstrated axonal features, being largely parallel in orientation and predominantly spaced one to two microtubule diameters apart, suggesting the presence of microtubule-bound spacer molecules. Testis microtubule-associated proteins (MAPs) were isolated by a taxol, salt elution procedure. Testis MAPs promoted microtubule assembly, but to a lesser degree than brain MAPs. High molecular weight MAPs, similar in electrophoretic mobilities to brain MAP-1 and MAP-2, were prominent components of total testis MAPs, though no shared immunoreactivity was detected between testis and brain high molecular weight MAPs using both polyclonal and monoclonal antibodies. Unlike brain high molecular weight MAPs, testis high molecular weight MAPs were not heat stable. Testis MAP composition, studied on postnatal days 5, 10, 15, and 24 and in the adult, changed dramatically during ontogeny. However, the expression of the major testis high molecular weight MAP, called HMW-2, was constitutive and independent of the development of mature germ cells. The Sertoli cell origin of HMW-2 was confirmed by identifying this protein as the major MAP found in an enriched Sertoli cell preparation and in two rat models of testicular injury characterized by germ cell depletion. HMW-2 was selectively released from testis microtubules by ATP and co-purified by sucrose density gradient centrifugation with MAP-1C, a neuronal cytoplasmic dynein. The inhibition of the microtubule-activated ATPase activity of HMW-2 by vanadate and erythro-(2-hydroxy-3-nonyl)adenine and its proteolytic breakdown by vanadate-dependent UV photocleavage confirmed the dynein-like nature of HMW-2. As demonstrated by this study, the neuronal and Sertoli cell cytoskeletons share morphological, structural and functional properties.

scholarly journals Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes

2010 ◽  
Vol 44 (4) ◽  
pp. 195-201 ◽  
Author(s):  
Samantha Gardner ◽  
Emmanouil Stavrou ◽  
Patricia E Rischitor ◽  
Elena Faccenda ◽  
Adam J Pawson
Keyword(s):  
Signal Transduction ◽  
Gnrh Receptor ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Key Players ◽  
Canonical Wnt ◽  
Recent Demonstration

The binding of GnRH to its receptor on pituitary gonadotropes leads to the targeting of a diverse array of signalling mediators. These mediators drive multiple signal transduction pathways, which in turn regulate a variety of cellular processes, including the biosynthesis and secretion of the gonadotropins LH and FSH. Advances in our understanding of the mechanisms and signalling pathways that are recruited to regulate gonadotrope function are continually being made. This review will focus on the recent demonstration that key mediators of the canonical Wnt signalling pathway are targeted by GnRH in gonadotropes, and that these may play essential roles in regulating the expression of many of the key players in gonadotrope biology, including the GnRH receptor and the gonadotropins.

scholarly journals HMGXB4 Targets Sleeping Beauty Transposition to Vertebrate Germinal Stem Cells

2020 ◽  
Author(s):  
Anantharam Devaraj ◽  
Manvendra Singh ◽  
Suneel Narayanavari ◽  
Guo Yong ◽  
Jiaxuan Wang ◽  
...  
Keyword(s):  
Domain Boundary ◽  
Sleeping Beauty ◽  
Chromatin Domain ◽  
Germline Development ◽  
Cell Stage ◽  
Cellular Processes ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory ◽  
Germ Cell Specification ◽  
Genome Activation

AbstractTransposons are parasitic genetic elements that frequently hijack key cellular processes of the host. HMGXB4 is a Wnt signalling-associated HMG-box protein, previously identified as a transcriptional regulating host factor of Sleeping Beauty (SB) transposition. Here, we establish that HMGXB4 is highly expressed from the zygote stage, and declines after transcriptional genome activation. Nevertheless, HMGXB4 is activated by its own promoter at 4-cell stage, responding to the parental-to-zygotic transition, marks stemness, and maintains its expression during germ cell specification. The HMGXB4 promoter is located at an active chromatin domain boundary. As a vertebrate-specific modulator of SETD1A and NuRF complexes, HMGXB4 links histone H3K4 methyltransferase- and ATP-dependent nucleosome remodelling activities. The expression of HMGXB4 is regulated by the KRAB-ZNF/TRIM28 epigenetic repression machinery. A post-transcriptional modification by SUMOylation diminishes its transcriptional activator function and regulates its nucleolar trafficking. Collectively, HMGXB4 positions SB transposition into an elaborate stem cell-specific transcriptional regulatory mechanism that is active during early embryogenesis and germline development, thereby potentiating heritable transposon insertions in the germline.

Neospora caninum cytoplasmic dynein LC8 light chain 2 (NcDYNLL2) is differentially produced by pathogenically distinct isolates and regulates the host immune response

Parasitology ◽  
2018 ◽  
Vol 146 (5) ◽  
pp. 588-595 ◽  
Author(s):  
Lili Cao ◽  
Raymond Fetterer ◽  
Guanggang Qu ◽  
Xichen Zhang ◽  
Wenbin Tuo
Keyword(s):  
Light Chain ◽  
Neospora Caninum ◽  
Calcium Ionophore ◽  
Cytoplasmic Dynein ◽  
Secretory Protein ◽  
Amino Acid Sequences ◽  
Interleukin 12 ◽  
Cellular Processes ◽  
Genetic Level ◽  
Microarray Studies

AbstractNeospora caninum is the causative agent of bovine neosporosis. A N. caninum cytoplasmic dynein LC8 light chain (NcDYNLL) protein was characterized in this study. Cytoplasmic dyneins, including DYNLLs, belong to the microtubule minus-end-directed motor proteins and are involved in many cellular processes. Previous microarray studies revealed that NcDYNLL was downregulated in the non-pathogenic clone, Ncts-8, when compared with the wild-type NC1 isolate. The present study showed that DYNLLs from different species are highly conserved (>85% identity), and the NcDYNLL belongs to the DYNLL2 family. NcDYNLL2 and Toxoplasma gondii DYNLL2 have identical amino acid sequences, although they are slightly divergent at the genetic level (89% identity). NcDYNLL2 was cloned and expressed in Escherichia coli and purified. NcDYNLL2 was identified in soluble and insoluble fractions of tachyzoite lysate. As expected, soluble NcDYNLL2 was lower in the Ncts-8 lysate when compared with that of NC1 isolate. NcDYNLL2 release by the tachyzoites was low; however, it was increased when tachyzoites were treated with either calcium ionophore or ethanol. The data indicate that NcDYNLL2 may be actively secreted at low levels, but the secretion was upregulated by agents that also augment microneme protein secretions. Immunostaining of NcDYNLL2 in isolated and intracellular Neospora tachyzoites showed a diffuse distribution pattern. Furthermore, rNcDYNLL2 was internalized by the host immune cells and stimulated tumour necrosis factor-α) and interleukin-12 (IL-12) production by murine dendritic cells. Taken together, these results suggest that NcDYNLL2 is a secretory protein that cross-regulates host immunity.

scholarly journals Preventing farnesylation of the dynein adaptor Spindly contributes to the mitotic defects caused by farnesyltransferase inhibitors

2015 ◽  
Vol 26 (10) ◽  
pp. 1845-1856 ◽  
Author(s):  
Andrew J. Holland ◽  
Rita M. Reis ◽  
Sherry Niessen ◽  
Cláudia Pereira ◽  
Douglas A. Andres ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Cytoplasmic Dynein ◽  
Molecular Replacement ◽  
Farnesyltransferase Inhibitors ◽  
Checkpoint Signaling ◽  
Cellular Processes ◽  
Chromosome Congression ◽  
Mitotic Abnormalities ◽  
Clinical Interest ◽  
Insight Into

The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore proteins CENP-E and CENP-F, which are involved in chromosome congression and spindle assembly checkpoint signaling. Here we identify the cytoplasmic dynein adaptor Spindly as an additional component of the outer kinetochore that is modified by farnesyltransferase (FTase). We show that farnesylation of Spindly is essential for its localization, and thus for the proper localization of dynein and its cofactor dynactin, to prometaphase kinetochores and that Spindly kinetochore recruitment is more severely affected by FTase inhibition than kinetochore recruitment of CENP-E and CENP-F. Molecular replacement experiments show that both Spindly and CENP-E farnesylation are required for efficient chromosome congression. The identification of Spindly as a new mitotic substrate of FTase provides insight into the causes of the mitotic phenotypes observed with FTase inhibitors.

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