Cell Cycle Regulation of Myosin-V by Calcium/Calmodulin-Dependent Protein Kinase II

Karcher, Ryan L.; Roland, Joseph T.; Zappacosta, Francessca; Huddleston, Michael J.; Annan, Roland S.; Carr, Steven A.; Gelfand, Vladimir I.

doi:10.1126/science.1061086

Cited by 138 publications

(108 citation statements)

References 29 publications

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“…Our results suggest a possible function for Kap3 phosphorylation in these processes. Previous studies in which phosphorylation of the myosin-V and KIF17 motors by calcium/calmodulin-dependent protein kinase II were suggested to control docking of cargo (Karcher et al, 2001;Guillaud et al, 2008) support our hypothesis. Identification of Kap3 phosphorylation site(s) is the next critical step to address these issues.…”

Section: Discussionsupporting

confidence: 78%

Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion

et al. 2008

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Recent studies have demonstrated essential functions for KIF3, a microtubule-directed protein motor, in subcellular transport of several cancer-related proteins, including the b-catenin-cadherin(s) complex. In this study, we report identification of the protein-phosphatase Dusp26 as a novel regulator of the KIF3 motor. Here we undertake yeast two-hybrid screening and identify Kif3a, a motor subunit of the KIF3 heterotrimeric complex, as a novel Dusp26-binding protein. Co-immunoprecipitation and colocalization experiments revealed that Dusp26 associates not only with Kif3a, but also with Kap3, another subunit of the KIF3 complex. Dephosphorylation experiments in vitro and analysis using mutant forms of Dusp26 in intact cells strongly suggested that Dusp26 is recruited to the KIF3 motor mainly by interaction with Kif3a, and thereby dephosphorylates Kap3. Forced expression of Dusp26, but not its catalytically inactive mutant, promoted distribution of b-catenin/N-cadherin, an established KIF3 cargo, to cell-cell junction sites, resulting in increased cell-cell adhesiveness. We also showed that Dusp26 mRNA expression was downregulated in human glioblastoma samples. These results suggest previously unidentified functions of Dusp26 in intracellular transport and cell-cell adhesion. Downregulation of Dusp26 may contribute to malignant phenotypes of glioma.

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Section: Discussionsupporting

confidence: 78%

Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion

et al. 2008

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“…S1A). It contains the serine S1650 in mouse Myo5A, whose phosphorylation by calcium/calmodulin-dependent protein kinase II results in its dissociation from melanosomes (19). In contrast, the insulin-stimulated phosphorylation of the same residue by Akt2 enhances the Myo5A-mediated transport of GLUT4 to the plasma membrane in adipocytes (20).…”

Section: Resultsmentioning

confidence: 99%

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Pylypenko

Attanda

Gauquelin

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

108

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Specific recognition of the cargo that molecular motors transport or tether to cytoskeleton tracks allows them to perform precise cellular functions at particular times and positions in cells. However, very little is known about how evolution has favored conservation of functions for some isoforms, while also allowing for the generation of new recognition sites and specialized cellular functions. Here we present several crystal structures of the myosin Va or the myosin Vb globular tail domain (GTD) that gives insights into how the motor is linked to the recycling membrane compartments via Rab11 or to the melanosome membrane via recognition of the melanophilin adaptor that binds to Rab27a. The structures illustrate how the Rab11-binding site has been conserved during evolution and how divergence at another site of the GTD allows more specific interactions such as the specific recognition of melanophilin by the myosin Va isoform. With atomic structural insights, these structures also show how either the partner or the GTD structural plasticity upon association is critical for selective recruitment of the motor.GTPases | DIL motif | Rab effector | intracellular traffic D irected movement is essential for life, and cytoskeletonbased motors generate mechanical force and motion to precisely organize the cell. Their coordinated actions allow them to play key roles in nearly every physiological process. Class V myosins (Myo5) and the related plant class XI myosins are a group of multifunctional actin-based nanomotors that have evolved from one of the three ancient myosin subfamilies (1). The motor domain and extended lever arm of these myosins is followed by a coiled coil dimerizing region and the C-terminal globular tail domain (GTD) that primarily plays a role in selective cargo recruitment. Little is known, however, about how this GTD sequence has evolved to serve both a role in regulation of the motor activity (2, 3) and specific recruitment of the motor, which is critical to control precisely in space and time when the motor is activated for different cellular functions.

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“…These interactions may play a dual role: (i) to deliver newly arrived vesicles to "holding" sites prior to release; (ii) to tether them prior to the arrival of a stimulatory signal (usually Ca 2+ ). Interestingly, reversible interactions between melanosomes and myoVa have been demonstrated [88] and shown to be regulated by Ca 2+ -dependent phosphorylation mediated by calmodulin kinase II [45]. In beta cells, the Ca 2+ trigger may lead to the dissociation of myoVa from its tethering site and the collapse of the actin network, thus liberating vesicles for fusion (Fig.…”

Section: Glucose-stimulated Insulin Secretion Is Biphasic: Visualisatmentioning

confidence: 98%

“…net loss of carbon atoms from the cycle), for example for amino acid biosynthesis [36]. Moreover, the generation by mitochondria of citrate and the production in the cytosol of NADPH by the action of malic enzyme may also be important for glucose signalling [44,45], although presently the downstream mechanisms are unclear. On the other hand, by increasing cytosolic malonyl-CoA levels, glucose appears to inhibit the β-oxidation of fatty acids, and the consequent accumulation of acyl-CoA in the cytosol may enhance insulin release [46].…”

Section: Introductionmentioning

confidence: 99%

Visualising insulin secretion. The Minkowski Lecture 2004

Rutter

2004

Diabetologia

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Insulin secretion from pancreatic islet beta cells is a tightly regulated process, under the close control of blood glucose concentrations, neural inputs and circulating hormones. Defects in glucose-triggered insulin secretion, possibly exacerbated by a decrease in beta cell mass, are ultimately responsible for the development of type 2 diabetes. A full understanding of the mechanisms by which glucose and other nutrients trigger insulin secretion will probably be essential to allow for the development of new therapies of type 2 diabetes and for the derivation of "artificial" beta cells from embryonic stem cells as a treatment for type 1 diabetes. I focus here on recent developments in our understanding of beta cell glucose sensing, achieved in part through the development of recombinant targeted probes (luciferase, green fluorescent protein) that allow islet beta cell metabolism and Ca 2+ handling to be imaged in situ in the intact islet with single cell resolution. Combined with classical biochemistry, these techniques show that the beta cell is uniquely poised, thanks to the expression of low levels of lactate dehydrogenase and plasma membrane lactate/monocarboxylate transporters, to channel glucose carbons towards oxidative metabolism, ATP synthesis and inhibition of AMP-activated protein kinase, a newly defined regulator of insulin release. I also discuss the molecular basis of the recruitment of secretory vesicles to the cell surface, analysed by the use of new imaging techniques including total internal reflection of fluorescence, as well as the "nanomechanics" of the exocytotic event itself.

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Cell Cycle Regulation of Myosin-V by Calcium/Calmodulin-Dependent Protein Kinase II

Cited by 138 publications

References 29 publications

Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion

Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Visualising insulin secretion. The Minkowski Lecture 2004

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