scholarly journals AMP-activated protein kinase regulates cytoplasmic dynein behavior and contributes to neuronal migration in the developing neocortex

Development ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. dev187310
Author(s):  
Yasuki Naito ◽  
Naoyuki Asada ◽  
Minh Dang Nguyen ◽  
Kamon Sanada
Keyword(s):  
Protein Kinase ◽  
Neuronal Migration ◽  
Pyramidal Neurons ◽  
Resistant Mutant ◽  
Cytoplasmic Dynein ◽  
Radial Migration ◽  
Dynein Intermediate Chain ◽  
Microtubule Motor ◽  
Developing Neocortex ◽  
Amp Activated Protein Kinase

ABSTRACTThe microtubule motor cytoplasmic dynein contributes to radial migration of newborn pyramidal neurons in the developing neocortex. Here, we show that AMP-activated protein kinase (AMPK) mediates the nucleus-centrosome coupling, a key process for radial neuronal migration that relies on dynein. Depletion of the catalytic subunit of AMPK in migrating neurons impairs this coupling as well as neuronal migration. AMPK shows overlapping subcellular distribution with cytoplasmic dynein and the two proteins interact with each other. Pharmacological inhibition or activation of AMPK modifies the phosphorylation states of dynein intermediate chain (DIC) and dynein functions. Furthermore, AMPK phosphorylates DIC at Ser81. Expression of a phospho-resistant mutant of DIC retards neuronal migration in a similar way to AMPK depletion. Conversely, expression of the phospho-mimetic mutant of DIC alleviates impaired neuronal migration caused by AMPK depletion. Thus, AMPK-regulated dynein function via Ser81 DIC phosphorylation is crucial for radial neuronal migration.

scholarly journals The Gene for the Intermediate Chain Subunit of Cytoplasmic Dynein Is Essential in Drosophila

Genetics ◽  
2002 ◽  
Vol 162 (3) ◽  
pp. 1211-1220 ◽  
Author(s):  
Kristin L M Boylan ◽  
Thomas S Hays
Keyword(s):  
Intracellular Transport ◽  
De Novo ◽  
Cytoplasmic Dynein ◽  
Chain Gene ◽  
Temperature Sensitive ◽  
Wing Development ◽  
Dynein Motor ◽  
Dynein Intermediate Chain ◽  
Microtubule Motor ◽  
Intermediate Chain

Abstract The microtubule motor cytoplasmic dynein powers a variety of intracellular transport events that are essential for cellular and developmental processes. A current hypothesis is that the accessory subunits of the dynein complex are important for the specialization of cytoplasmic dynein function. In a genetic approach to understanding the range of dynein functions and the contribution of the different subunits to dynein motor function and regulation, we have identified mutations in the gene for the cytoplasmic dynein intermediate chain, Dic19C. We used a functional Dic transgene in a genetic screen to recover X-linked lethal mutations that require this transgene for viability. Three Dic mutations were identified and characterized. All three Dic alleles result in larval lethality, demonstrating that the intermediate chain serves an essential function in Drosophila. Like a deficiency that removes Dic19C, the Dic mutations dominantly enhance the rough eye phenotype of Glued1, a dominant mutation in the gene for the p150 subunit of the dynactin complex, a dynein activator. Additionally, we used complementation analysis to identify an existing mutation, shortwing (sw), as an allele of the dynein intermediate chain gene. Unlike the Dic alleles isolated de novo, shortwing is homozygous viable and exhibits recessive and temperature-sensitive defects in eye and wing development. These phenotypes are rescued by the wild-type Dic transgene, indicating that shortwing is a viable allele of the dynein intermediate chain gene and revealing a novel role for dynein function during wing development.

scholarly journals Apoptotic Cleavage of Cytoplasmic Dynein Intermediate Chain and P150GluedStops Dynein-Dependent Membrane Motility

2001 ◽  
Vol 153 (7) ◽  
pp. 1415-1426 ◽  
Author(s):  
Jon D. Lane ◽  
Maïlys A.S. Vergnolle ◽  
Philip G. Woodman ◽  
Victoria J. Allan
Keyword(s):  
Mammalian Cells ◽  
Cytoplasmic Dynein ◽  
Animal Cells ◽  
Dynein Intermediate Chain ◽  
Egg Extracts ◽  
Microtubule Motor ◽  
Xenopus Egg ◽  
Xenopus Egg Extracts ◽  
Dynactin Complex ◽  
Intermediate Chains

Cytoplasmic dynein is the major minus end–directed microtubule motor in animal cells, and associates with many of its cargoes in conjunction with the dynactin complex. Interaction between cytoplasmic dynein and dynactin is mediated by the binding of cytoplasmic dynein intermediate chains (CD-IC) to the dynactin subunit, p150Glued. We have found that both CD-IC and p150Glued are cleaved by caspases during apoptosis in cultured mammalian cells and in Xenopus egg extracts. Xenopus CD-IC is rapidly cleaved at a conserved aspartic acid residue adjacent to its NH2-terminal p150Glued binding domain, resulting in loss of the otherwise intact cytoplasmic dynein complex from membranes. Cleavage of CD-IC and p150Glued in apoptotic Xenopus egg extracts causes the cessation of cytoplasmic dynein–driven endoplasmic reticulum movement. Motility of apoptotic membranes is restored by recruitment of intact cytoplasmic dynein and dynactin from control cytosol, or from apoptotic cytosol supplemented with purified cytoplasmic dynein–dynactin, demonstrating the dynamic nature of the association of cytoplasmic dynein and dynactin with their membrane cargo.

scholarly journals Cytoplasmic Dynein Regulation by Subunit Heterogeneity and Its Role in Apical Transport

2001 ◽  
Vol 153 (7) ◽  
pp. 1499-1510 ◽  
Author(s):  
Andrew W. Tai ◽  
Jen-Zen Chuang ◽  
Ching-Hwa Sung
Keyword(s):  
Mdck Cells ◽  
Cytoplasmic Dynein ◽  
Apical Surface ◽  
Dynein Light Chain ◽  
Madin Darby Canine Kidney ◽  
Dynein Intermediate Chain ◽  
Microtubule Motor ◽  
Polarized Epithelia ◽  
Darby Canine Kidney ◽  
Canine Kidney

Despite the existence of multiple subunit isoforms for the microtubule motor cytoplasmic dynein, it has not yet been directly shown that dynein complexes with different compositions exhibit different properties. The 14-kD dynein light chain Tctex-1, but not its homologue RP3, binds directly to rhodopsin's cytoplasmic COOH-terminal tail, which encodes an apical targeting determinant in polarized epithelial Madin-Darby canine kidney (MDCK) cells. We demonstrate that Tctex-1 and RP3 compete for binding to dynein intermediate chain and that overexpressed RP3 displaces endogenous Tctex-1 from dynein complexes in MDCK cells. Furthermore, replacement of Tctex-1 by RP3 selectively disrupts the translocation of rhodopsin to the MDCK apical surface. These results directly show that cytoplasmic dynein function can be regulated by its subunit composition and that cytoplasmic dynein is essential for at least one mode of apical transport in polarized epithelia.

scholarly journals A Molecular Genetic Analysis of the Interaction between the Cytoplasmic Dynein Intermediate Chain and the Glued (Dynactin) Complex

2000 ◽  
Vol 11 (11) ◽  
pp. 3791-3803 ◽  
Author(s):  
Kristin Boylan ◽  
Madeline Serr ◽  
Tom Hays
Keyword(s):  
Molecular Genetic ◽  
Cytoplasmic Dynein ◽  
Molecular Genetic Analysis ◽  
Chain Gene ◽  
Cellular Functions ◽  
Dynein Intermediate Chain ◽  
Biochemical Interaction ◽  
Microtubule Motor ◽  
Regulatory Complex ◽  
Intermediate Chain

The microtubule motor cytoplasmic dynein performs multiple cellular functions; however, the regulation and targeting of the motor to different cargoes is not well understood. A biochemical interaction between the dynein intermediate chain subunit and the p150-Glued component of the dynein regulatory complex, dynactin, has supported the hypothesis that the intermediate chain is a key modulator of dynein attachment to cellular cargoes. In this report, we identify multiple intermediate chain polypeptides that cosediment with the 19S dynein complex and two differentially expressed transcripts derived from the single cytoplasmic dynein intermediate chain (Cdic) gene that differ in the 3′ untranslated region sequence. These results support previous observations of multiple Cdic gene products that may contribute to the specialization of dynein function. Most significantly, we provide genetic evidence that the interaction between the dynein intermediate chain and p150-Glued is functionally relevant. We use a genomic Cdic transgene to show that extra copies of the dynein intermediate chain gene act to suppress the rough eye phenotype of the mutant Glued 1, a mutation in the p150-Glued subunit of dynactin. Furthermore, we show that the interaction between the dynein intermediate chain and p150-Glued is dependent on the dosage of the Cdic gene. This result suggests that the dynein intermediate chain may be a limiting component in the assembly of the dynein complex and that the regulation of the interaction between the dynein intermediate chain and dynactin is critical for dynein function.

scholarly journals FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

2016 ◽  
Vol 113 (45) ◽  
pp. E7087-E7096 ◽  
Author(s):  
Ricardo H. Paap ◽  
Saskia Oosterbroek ◽  
Cindy M. R. J. Wagemans ◽  
Lars von Oerthel ◽  
Raymond D. Schellevis ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Cortical Development ◽  
Forkhead Transcription Factor ◽  
Altered Expression ◽  
Radial Migration ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Developing Neocortex

The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/− and FoxO6−/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6. We then show that FoxO6 binds to DAF-16–binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression. Finally, ectopic Plxna4 expression restores radial migration in FoxO6+/− and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.

Chronic activation of AMP-activated protein kinase increases monocarboxylate transporter 2 and 4 expression in skeletal muscle

2017 ◽  
Vol 95 (8) ◽  
pp. 3552
Author(s):  
E. M. England ◽  
H. Shi ◽  
S. K. Matarneh ◽  
E. M. Oliver ◽  
E. T. Helm ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Monocarboxylate Transporter ◽  
Chronic Activation ◽  
Amp Activated Protein Kinase
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