Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian oocytes undergo an asymmetrical first meiotic division, extruding half of their chromosomes in a small polar body to preserve maternal resources for embryonic development. To divide asymmetrically, mammalian oocytes relocate chromosomes from the center of the cell to the cortex, but little is known about the underlying mechanisms. Here, we show that upon the elevation of intracellular cAMP level, mouse oocytes produced two daughter cells with similar sizes. This symmetrical cell division could be rescued by the inhibition of PKA, a cAMP-dependent protein kinase. Live cell imaging revealed that a symmetrically localized cleavage furrow resulted in symmetrical cell division. Detailed analyses demonstrated that symmetrically localized cleavage furrows were caused by the inappropriate central positioning of chromosome clusters at anaphase onset, indicating that chromosome cluster migration was impaired. Notably, high intracellular cAMP reduced myosin II activity, and the microinjection of phospho-myosin II antibody into the oocytes impeded chromosome migration and promoted symmetrical cell division. Our results support the hypothesis that cAMP plays a role in regulating asymmetrical cell division by modulating myosin II activity during mouse oocyte meiosis I, providing a novel insight into the regulation of female gamete formation in mammals.
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PMID:Regulation of asymmetrical cytokinesis by cAMP during meiosis I in mouse oocytes. 2225 67

The acquisition of goal-directed action requires encoding of the association between an action and its specific consequences or outcome. At a neural level, this encoding has been hypothesized to involve a prefrontal corticostriatal circuit involving the projection from the prelimbic cortex (PL) to the posterior dorsomedial striatum (pDMS); however, no direct evidence for this claim has been reported. In a series of experiments, we performed functional disconnection of this pathway using targeted lesions of the anterior corpus callosum to disrupt contralateral corticostriatal projections with asymmetrical lesions of the PL and/or pDMS to block plasticity in this circuit in rats. We first demonstrated that unilaterally blocking the PL input to the pDMS prevented the phosphorylation of extracellular signal-related kinase/mitogen activated protein kinase (pERK/pMAPK) induced by instrumental training. Next, we used a full bilateral disconnection of the PL from the pDMS and assessed goal-directed action using an outcome-devaluation test. Importantly, we found evidence that rats maintaining an ipsilateral and/or contralateral connection between the PL and the pDMS were able to acquire goal-directed actions. In contrast, bilateral PL-pDMS disconnection abolished the acquisition of goal-directed actions. Finally, we used a temporary pharmacological disconnection to disrupt PL inputs to the pDMS by infusing the NMDA antagonist dl-2-amino-5-phosphonopentanoic acid into the pDMS during instrumental training and found that this manipulation also disrupted goal-directed learning. These results establish that, in rats, the acquisition of new goal-directed actions depends on a prefrontal-corticostriatal circuit involving a connection between the PL and the pDMS.SIGNIFICANCE STATEMENT It has been hypothesized that the prelimbic cortex (PL) and posterior dorsomedial striatum (pDMS) in rodents interact in a corticostriatal circuit to mediate goal-directed learning. However, no direct evidence supporting this claim has been reported. Using targeted lesions, we performed functional disconnection of the PL-pDMS pathway to assess its role in goal-directed learning. In the first experiment, we demonstrated that PL input to the pDMS is necessary for instrumental training-induced neuronal activity. Next, we disrupted ipsilateral, contralateral, or bilateral PL-pDMS connections and found that only bilateral PL-pDMS disconnection disrupted the acquisition of goal-directed actions, a finding we replicated in our final study using a pharmacological disconnection procedure.
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PMID:Prefrontal Corticostriatal Disconnection Blocks the Acquisition of Goal-Directed Action. 2930 72

Progressive movement of spermatozoa has conventionally been regarded as a good indicator of motility. However, bull spermatozoa exhibit two types of progressive movement: progressive/planar movement without rotation and progressive/helical movement with rotation. The aim of this study was to reconsider the evaluation criteria of bull ejaculated sperm motility in the context of rotation. Here, we compared the movement patterns of ejaculated spermatozoa with relatively high and low protein kinase A (PKA)-mediated signaling activities, because sperm motility is positively regulated by PKA-mediated signaling activities. We prepared sperm samples with high and low PKA-mediated signaling activities by suspending spermatozoa in media containing either the stimulator (NaHCO3) or inhibitor (KH-7) of adenylyl cyclase 10, and we then investigated movement patterns and relative velocities using a microscopic high-speed camera and recording system. In the control medium without NaHCO3 and KH-7, most spermatozoa exhibited round/planar movement without rotation and asymmetrical bends in the principal pieces. NaHCO3 significantly promoted changes in movement patterns from round/planar movement to progressive/planar movement (without rotation) as well as symmetrization of flagellar bends and increased relative velocities. KH-7 significantly increased spermatozoa exhibiting progressive/helical movement (with rotation), decreased relative velocities, and symmetrized flagellar bends with a reduction in their size. These indicate that progressive/planar movement (without rotation) and fast movement characterize the movement patterns of bull ejaculated spermatozoa with high PKA-mediated signaling activities. A sign of reduced PKA-mediated signaling activity is not only slow movement but also helical movement (with rotation). Thus, it is beneficial to add a new parameter of "rotation" to the evaluation criteria of bull ejaculated sperm motility.
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PMID:Reconsideration of the evaluation criteria for bull ejaculated sperm motility in the context of rotation. 2995 39

During neocortical development, there are two important events, including expansion of the neural progenitor pool through symmetric divisions, and generation of neurons via asymmetrical divisions that lead to a serial process of neuronal polarization, migration, and layer-type specific phenotype acquisition. The mechanisms underlying these processes remain poorly elucidated. Here, we show that the transcription factor Zeb1 regulates the orientation of the cleavage plane of dividing neural progenitors, neuronal polarity, and migration. Upon Zeb1 removal, the cleavage plane of mitotic neural progenitors fails to orientate vertically, resulting in random orientation and premature neuronal differentiation. Consequently, these extra number of precociously produced neurons migrate aberrantly to the upper layer. Mechanistically, we show that Zeb1 suppresses Pak3, a p21-activated serine/threonine protein kinase, through formation of a functional repressing complex together with methyltransferase PRMT5 and Pak3. Our results reveal that Zeb1 plays an essential role in neocortical development and may provide insights into the mechanisms responsible for cortical developmental diseases.
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PMID:Zeb1 is important for proper cleavage plane orientation of dividing progenitors and neuronal migration in the mouse neocortex. 3085 7


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