scholarly journals Egalitarian binding partners, Dynein Light Chain and Bicaudal-D, act sequentially to link mRNA to the Dynein motor

2019 ◽  
Author(s):  
Chandler H. Goldman ◽  
Rajalakshmi Veeranan-Karmegam ◽  
Hannah Neiswender ◽  
Graydon B. Gonsalvez
Keyword(s):  
Light Chain ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Mrna Localization ◽  
Null Alleles ◽  
Dynein Light Chain ◽  
Binding Partners ◽  
Dynein Motor ◽  
Microtubule Motors

AbstractA widely conserved mechanism of polarity establishment is the localization of mRNA to specific cellular regions. While it is clear that many mRNAs are transported to their destinations along microtubule tracks, much less is known regarding the mechanism by which these mRNAs are linked to microtubule motors. The RNA binding protein Egalitarian (Egl) is necessary for localization of several mRNAs in Drosophila oocytes and embryos. In addition to binding RNA, Egl also interacts with Dynein light chain (Dlc) and Bicaudal-D (BicD). The role of Dlc and BicD in mRNA localization has remained elusive. Like Egl, both proteins are required for oocyte specification. Null alleles in these genes result in an oogenesis block. In this report, we used an innovative approach to overcome the oogenesis block. Our findings reveal that the primary function of Dlc is to promote Egl dimerization. Loss of dimerization compromises the ability of Egl to bind RNA. Consequently, Egl is not bound to cargo, and is not able to efficiently associate with BicD and the Dynein motor. Our results therefore identify the key molecular steps required for assembling a localization competent mRNP.

scholarly journals Functional interaction between dynein light chain and intermediate chain is required for mitotic spindle positioning

2011 ◽  
Vol 22 (15) ◽  
pp. 2690-2701 ◽  
Author(s):  
Melissa D. Stuchell-Brereton ◽  
Amanda Siglin ◽  
Jun Li ◽  
Jeffrey K. Moore ◽  
Shubbir Ahmed ◽  
...  
Keyword(s):  
Light Chain ◽  
Direct Evidence ◽  
Retrograde Transport ◽  
Cytoplasmic Dynein ◽  
Dynein Light Chain ◽  
Spindle Positioning ◽  
Dynein Motor ◽  
Intermediate Chains ◽  
Activator Complex

Cytoplasmic dynein is a large multisubunit complex involved in retrograde transport and the positioning of various organelles. Dynein light chain (LC) subunits are conserved across species; however, the molecular contribution of LCs to dynein function remains controversial. One model suggests that LCs act as cargo-binding scaffolds. Alternatively, LCs are proposed to stabilize the intermediate chains (ICs) of the dynein complex. To examine the role of LCs in dynein function, we used Saccharomyces cerevisiae, in which the sole function of dynein is to position the spindle during mitosis. We report that the LC8 homologue, Dyn2, localizes with the dynein complex at microtubule ends and interacts directly with the yeast IC, Pac11. We identify two Dyn2-binding sites in Pac11 that exert differential effects on Dyn2-binding and dynein function. Mutations disrupting Dyn2 elicit a partial loss-of-dynein phenotype and impair the recruitment of the dynein activator complex, dynactin. Together these results indicate that the dynein-based function of Dyn2 is via its interaction with the dynein IC and that this interaction is important for the interaction of dynein and dynactin. In addition, these data provide the first direct evidence that LC occupancy in the dynein motor complex is important for function.

scholarly journals Egalitarian is a selective RNA-binding protein linking mRNA localization signals to the dynein motor

2009 ◽  
Vol 23 (13) ◽  
pp. 1546-1558 ◽  
Author(s):  
M. Dienstbier ◽  
F. Boehl ◽  
X. Li ◽  
S. L. Bullock
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mrna Localization ◽  
Dynein Motor

scholarly journals The Egalitarian binding partners Dynein light chain and Bicaudal-D act sequentially to link mRNA to the Dynein motor

Development ◽  
2019 ◽  
Vol 146 (15) ◽  
pp. dev176529 ◽  
Author(s):  
Chandler H. Goldman ◽  
Hannah Neiswender ◽  
Rajalakshmi Veeranan-Karmegam ◽  
Graydon B. Gonsalvez
Keyword(s):  
Light Chain ◽  
Dynein Light Chain ◽  
Binding Partners ◽  
Dynein Motor

scholarly journals Dynein light chain-dependent dimerization of Egalitarian is essential for maintaining oocyte fate in Drosophila.

2021 ◽  
Author(s):  
Hannah Neiswender ◽  
Chandler H Goldman ◽  
Rajalakshmi Veeranan-Karmegam ◽  
Graydon B. Gonsalvez
Keyword(s):  
Light Chain ◽  
Leucine Zipper ◽  
Three Dimensional ◽  
Mrna Localization ◽  
Binding Activity ◽  
Dynein Light Chain ◽  
Dynein Motor ◽  
Mutant Phenotypes ◽  
Mrna Binding

Egalitarian (Egl) is an RNA adaptor for the Dynein motor and is thought to link numerous, perhaps hundreds, of mRNAs with Dynein. Dynein, in turn, is responsible for the transport and localization of these mRNAs. Studies have shown that efficient mRNA binding by Egl requires the protein to dimerize. We recently demonstrated that Dynein light chain (Dlc) is responsible for facilitating the dimerization of Egl. Mutations in Egl that fail to interact with Dlc do not dimerize, and as such, are defective for mRNA binding. Consequently, this mutant does not efficiently associate with BicaudalD (BicD), the factor responsible for linking the Egl/mRNA complex with Dynein. In this report, we tested whether artificially dimerizing this Dlc-binding mutant using a leucine zipper would restore mRNA binding and rescue mutant phenotypes in vivo. Interestingly, we found that although artificial dimerization of Egl restored BicD binding, it only partially restored mRNA binding. As a result, Egl-dependent phenotypes, such as oocyte specification and mRNA localization, were only partially rescued. We hypothesize that Dlc-mediated dimerization of Egl results in a three-dimensional conformation of the Egl dimer that is best suited for mRNA binding. Although the leucine zipper restores Egl dimerization, it likely does not enable Egl to assemble into the conformation required for maximal mRNA binding activity.

scholarly journals Smooth muscle-specific HuR knockout induces defective autophagy and atherosclerosis

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Shanshan Liu ◽  
Xiuxin Jiang ◽  
Xiuru Cui ◽  
Jingjing Wang ◽  
Shangming Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Events ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Plaque Burden ◽  
Atherosclerotic Plaques ◽  
Ampk Activation ◽  
Homeostatic Regulation ◽  
Human Antigen R

AbstractHuman antigen R (HuR) is a widespread RNA-binding protein involved in homeostatic regulation and pathological processes in many diseases. Atherosclerosis is the leading cause of cardiovascular disease and acute cardiovascular events. However, the role of HuR in atherosclerosis remains unknown. In this study, mice with smooth muscle-specific HuR knockout (HuRSMKO) were generated to investigate the role of HuR in atherosclerosis. HuR expression was reduced in atherosclerotic plaques. As compared with controls, HuRSMKO mice showed increased plaque burden in the atherosclerotic model. Mechanically, HuR could bind to the mRNAs of adenosine 5′-monophosphate-activated protein kinase (AMPK) α1 and AMPKα2, thus increasing their stability and translation. HuR deficiency reduced p-AMPK and LC3II levels and increased p62 level, thereby resulting in defective autophagy. Finally, pharmacological AMPK activation induced autophagy and suppressed atherosclerosis in HuRSMKO mice. Our findings suggest that smooth muscle HuR has a protective effect against atherosclerosis by increasing AMPK-mediated autophagy.

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.

miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 4089-4098 ◽  
Author(s):  
F. Matsuzaki ◽  
T. Ohshiro ◽  
H. Ikeshima-Kataoka ◽  
H. Izumi
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Mrna Localization ◽  
Cell Cortex ◽  
Drosophila Embryogenesis ◽  
Cellular Asymmetry ◽  
Molecular Machinery ◽  
Cycle Dependent ◽  
Ganglion Mother Cell

When neuroblasts divide, prospero protein and mRNA segregate asymmetrically into the daughter neuroblast and sibling ganglion mother cell. miranda is known to localize prospero protein to the basal cell cortex of neuroblasts while the staufen RNA-binding protein mediates prospero mRNA localization. Here we show that miranda is required for asymmetric staufen localization in neuroblasts. Analyses using miranda mutants reveal that prospero and staufen interact with miranda under the same cell-cycle-dependent control. miranda thus acts to partition both prospero protein and mRNA. Furthermore, miranda localizes prospero and staufen to the basolateral cortex in dividing epithelial cells, which express the three proteins prior to neurogenesis. Our observations suggest that the epithelial cell and neuroblast (both of epithelial origin) share the same molecular machinery for creating cellular asymmetry.

scholarly journals Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

FEBS Open Bio ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1964-1976 ◽  
Author(s):  
Nirmala Tilija Pun ◽  
Amrita Khakurel ◽  
Aastha Shrestha ◽  
Sang‐Hyun Kim ◽  
Pil‐Hoon Park
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Cancer Cell Growth ◽  
Globular Adiponectin
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