Nuclear distribution element‐like 1 (Ndel1 or Nudel) was firstly described as a regulator of the cytoskeleton in microtubule and intermediate filament dynamics and microtubule‐based transport. Emerging evidence indicates that Ndel1 also serves as a docking platform for signaling proteins and modulates enzymatic activities (kinase, ATPase, oligopeptidase, GTPase). Through these structural and signaling functions, Ndel1 plays a role in diverse cellular processes (e.g., mitosis, neurogenesis, neurite outgrowth, and neuronal migration). Furthermore, Ndel1 is linked to the etiology of various mental illnesses and neurodegenerative disorders. In the present review, we summarize the physiological and pathological functions associated with Ndel1. We further advance the concept that Ndel1 interfaces GTPases‐mediated processes (endocytosis, vesicles morphogenesis/signaling) and cytoskeletal dynamics to impact cell signaling and behaviors. This putative mechanism may affect cellular functionalities and may contribute to shed light into the causes of devastating human diseases. © 2011 Wiley Periodicals, Inc.

The dimorphic transition of yeast to the hyphal form is regulated by the mitogen-activated protein kinase and cyclic AMP-dependent protein kinase A pathways in Saccharomyces cerevisiae. Signaling pathway-responsive transcription factors such as Ste12, Tec1, and Flo8 are known to mediate filamentation-specific transcription. We were interested in investigating the translational regulation of specific mRNAs during the yeast-tohyphal-form transition. Using polyribosome fractionation and RT-PCR analysis, we identified STE12, GPA2, and CLN1 as translation regulation target genes during filamentous growth. The transcript levels for these genes did not change, but their mRNAs were preferentially associated with polyribosomes during the hyphal transition. The intracellular levels of Ste12, Gpa2, and Cln1 proteins increased under hyphal-growth conditions. The increase in Ste12 protein level was partially blocked by mutations in the CAF20 and DHH1 genes, which encode an eIF4E inhibitor and a decapping activator, respectively. In addition, the caf20 and dhh1 mutations resulted in defects in filamentous growth. The filamentation defects caused by caf20 and dhh1 mutations were suppressed by STE12 overexpression. These results suggest that Caf20 and Dhh1 control yeast filamentation by regulating STE12 translation.The cellular morphology of diploid Saccharomyces cerevisiae frequently switches between the yeast and filamentous forms depending on nutritional signals (16). Several signal transduction modules, including the mitogen-activated protein kinase (MAPK) cascade and the cyclic AMP-dependent protein kinase A (PKA) pathway, are known to participate in this switch (14,21,31,36). The MAPK cascade involves Ste20, Ste11, Ste7, Kss1, and the transcription factors Ste12 and Tec1 (15,21,29,30). The PKA pathway involves Gpr1, Gpa2, Ras2, Tpk2, and the transcription factors Flo8 and Sfl1 (22,26,31,32). These signaling pathways control the transcription of a number of filamentation-specific genes, including FLO11 (19,23,29).Although the signaling pathways and transcriptional regulation of yeast filamentous growth have been studied in considerable detail, little is known about translational regulation related to the transition from the yeast to the filamentous form. In this study, we searched for specific mRNAs that are preferentially translated during the yeast-to-hyphal-form transition. Genome-wide analysis of mRNA translation profiles indicates that the loading of ribosomes onto individual mRNA species varies broadly (20, 28). The association of mRNA transcripts in polyribosomes reflects the rate of synthesis of their corresponding proteins (3, 45). By purifying polyribosome fractions and employing RT-PCR analysis, we found that the mRNA transcripts of STE12, GPA2, and CLN1 were preferentially recruited to polyribosomes during filamentation compared to during normal vegetative growth, even though their levels in the total cell extracts were not changed. Consistently, the protein levels of Ste12, Gpa2, and Cln1 also increased during...

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Background: Dysbindin and Disrupted-in-schizophrenia 1 (DISC1) are major schizophrenia susceptibility factors. Results: DISC1 enhances stability of dysbindin, which is critical for neurite outgrowth. Conclusion: Dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth. Significance: Our findings indicate the existence of a protein complex composed of multiple schizophrenia susceptibility factors functioning in a pathway for neurite outgrowth.

The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we revealed that the serine 321 residue (S321) in the third intracellular loop of DRD2 (D2i3) is a novel regulatory site of Cdk5. Cdk5-dependent phosphorylation of S321 in the D2i3 was observed in in vitro and cell culture systems. We further observed that the phosphorylation of S321 impaired the agonist-stimulated surface expression of DRD2 and decreased G protein coupling to DRD2. Moreover, the downstream cAMP pathway was affected in the heterologous system and in primary neuronal cultures from p35 knockout embryos likely due to the reduced inhibitory activity of DRD2. These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.

Cytoskeleton dynamics, membranes trafficking and positioning are essential for the proper functioning of any mammalian cell. The identification of the molecules and mechanisms that allow these cellular processes to interface is vital for understanding cell behaviors. Ndel1, the mammalian homolog of the Aspergillus nidulans NudE, organizes the cytoskeleton and regulates molecular motors, thereby impacting on the positioning of membranes. Hypothetically, Ndel1 can act in concert with enzymes controlling membrane trafficking (vesicle-mediated transport) per se, but this idea has never been investigated. We now report that a pool of Ndel1 associates directly with Dynamin 2 (Dyn2), a large cytosolic GTPase involved in the trafficking of the AMPA receptor subunit GluR1. In vitro, Ndel1 enhances Dyn2 GTPase activity in its unassembled and assembled forms, without promoting oligomerization of the enzyme. In cells, gain and loss of function of Ndel1 recapitulate the effects of overexpression of Dyn2 and Dyn2 dominant negative with reduced GTPase activity on the intracellular localization of GluR1, respectively, without affecting the stability of microtubules. Together, these results indicate that Ndel1 regulates Dyn2 GTPase activity and impacts GluR1-containing membranes distribution in a manner reminiscent of Dyn2.

This paper reports a stator shape optim for reducing the cogging torque of single-phase motor adopting an asymmetric air-gap to ma starting. Time step 2D-finite element analysis (FE out to analyze the characteristics of a single-phas motor. To reduce the cogging torque and maintai and torque, the Kriging model based on La sampling (LHS) and a genetic algorithm (GA) we optimal design result, the cogging torque on the was reduced. Finally, the analysis and optimal were confirmed by FEA and the experimental resu I.978-1-4799-5776-7/14/$31.00 ©2014 IEEE

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