Qian Chen

East China University of Science and Technology, Shanghai, Shanghai Shi, China

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Publications (17)103.42 Total impact

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    ABSTRACT: In mice, the compact hippocampal primordium is formed during the prenatal stage by early-generated neurons that migrate from the lateral ventricular zone. However, despite much being understood about the formation of the hippocampus, the molecular mechanisms that maintain the morphology of the hippocampal primordium after its formation remain to be characterized. β-catenin is a key factor of canonical Wnt signaling and also a component of adherens junctions. Previous embryonic deletion studies have demonstrated that β-catenin is required for early development and generation of granule cells. However, whether β-catenin is involved in the morphological maintenance of the hippocampus as a cell adhesion molecule is still unknown. Here, we report that perinatal deletion of β-catenin in postmitotic neurons and some radial glial cells of hippocampus using CamKIIα-iCre; β-catenin(flox/flox) conditional knockout mice, leads to the disorganization of the radial glial scaffold and consequentially severe defects in hippocampal morphology. We demonstrate that β-catenin is required for maintaining radial glial scaffold possibly via its well-known role in cell adhesion during the perinatal period. These findings provide essential advances into our understanding of the maintaince of the hippocampal primordium during the perinatal period.
    Neuroscience 10/2014; 284. DOI:10.1016/j.neuroscience.2014.08.055
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    ABSTRACT: Plant clathrin-mediated membrane trafficking is involved in many developmental processes as well as in responses to environmental cues. Previous studies have shown that clathrin-mediated endocytosis of the plasma membrane (PM) auxin transporter PIN-FORMED1 is regulated by the extracellular auxin receptor AUXIN BINDING PROTEIN1 (ABP1). However, the mechanisms by which ABP1 and other factors regulate clathrin-mediated trafficking are poorly understood. Here, we applied a genetic strategy and time-resolved imaging to dissect the role of clathrin light chains (CLCs) and ABP1 in auxin regulation of clathrin-mediated trafficking in Arabidopsis thaliana. Auxin was found to differentially regulate the PM and trans-Golgi network/early endosome (TGN/EE) association of CLCs and heavy chains (CHCs) in an ABP1-dependent but TRANSPORT INHIBITOR RESPONSE1/AUXIN-BINDING F-BOX PROTEIN (TIR1/AFB)-independent manner. Loss of CLC2 and CLC3 affected CHC membrane association, decreased both internalization and intracellular trafficking of PM proteins, and impaired auxin-regulated endocytosis. Consistent with these results, basipetal auxin transport, auxin sensitivity and distribution, and root gravitropism were also found to be dramatically altered in clc2 clc3 double mutants, resulting in pleiotropic defects in plant development. These results suggest that CLCs are key regulators in clathrin-mediated trafficking downstream of ABP1-mediated signaling and thus play a critical role in membrane trafficking from the TGN/EE and PM during plant development.
    The Plant Cell 02/2013; 25(2). DOI:10.1105/tpc.112.108373
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    ABSTRACT: Although the role of auxin in biotrophic pathogenesis has been extensively studied, relatively little is known about its role in plant resistance to necrotrophs. Arabidopsis thaliana mutants defective in different aspects of the auxin pathway are generally more susceptible than wild-type plants to the necrotrophic pathogen Alternaria brassicicola. We show that A. brassicicola infection up-regulates auxin biosynthesis and down-regulates the auxin transport capacities of infected plants, these effects being partially dependent on JA signaling. We also show that these effects of A. brassicicola infection together lead to an enhanced auxin response in host plants. Application of IAA and MeJA together synergistically induces the expression of defense marker genes PDF1.2 (PLANT DEFENSIN 1.2) and HEL (HEVEIN-LIKE), suggesting that enhancement of JA-dependent defense signaling may be part of the auxin-mediated defense mechanism involved in resistance to necrotrophic pathogens. Our results provide molecular evidence supporting the hypothesis that JA and auxin interact positively in regulating plant resistance to necrotrophic pathogens and that activation of auxin signaling by JA may contribute to plant resistance to necrotrophic pathogens.
    New Phytologist 06/2012; 195(4):872-82. DOI:10.1111/j.1469-8137.2012.04208.x
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    ABSTRACT: The root stem cell niche, which in the Arabidopsis thaliana root meristem is an area of four mitotically inactive quiescent cells (QCs) and the surrounding mitotically active stem cells, is critical for root development and growth. We report here that during jasmonate-induced inhibition of primary root growth, jasmonate reduces root meristem activity and leads to irregular QC division and columella stem cell differentiation. Consistently, jasmonate reduces the expression levels of the AP2-domain transcription factors PLETHORA1 (PLT1) and PLT2, which form a developmentally instructive protein gradient and mediate auxin-induced regulation of stem cell niche maintenance. Not surprisingly, the effects of jasmonate on root stem cell niche maintenance and PLT expression require the functioning of MYC2/JASMONATE INSENSITIVE1, a basic helix-loop-helix transcription factor that involves versatile aspects of jasmonate-regulated gene expression. Gel shift and chromatin immunoprecipitation experiments reveal that MYC2 directly binds the promoters of PLT1 and PLT2 and represses their expression. We propose that MYC2-mediated repression of PLT expression integrates jasmonate action into the auxin pathway in regulating root meristem activity and stem cell niche maintenance. This study illustrates a molecular framework for jasmonate-induced inhibition of root growth through interaction with the growth regulator auxin.
    The Plant Cell 09/2011; 23(9):3335-52. DOI:10.1105/tpc.111.089870
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    ABSTRACT: The subcellular distribution of the PIN-FORMED (PIN) family of auxin transporters plays a critical role in auxin gradient-mediated developmental processes, including lateral root formation and gravitropic growth. Here, we report two distinct aspects of CORONATINE INSENSITIVE 1 (COI1)- and AUXIN RESISTANT 1 (AXR1)-dependent methyl jasmonate (MeJA) effects on PIN2 subcellular distribution: at lower concentration (5 μM), MeJA inhibits PIN2 endocytosis, whereas, at higher concentration (50 μM), MeJA reduces PIN2 accumulation in the plasma membrane. We show that mutations of ASA1 (ANTHRANILATE SYNTHASE a1) and the TIR1/AFBs (TRANSPORT INHIBITOR RESPONSE 1/AUXIN-SIGNALING F-BOX PROTEINs) auxin receptor genes impair the inhibitory effect of 5 μM MeJA on PIN2 endocytosis, suggesting that a lower concentration of jasmonate inhibits PIN2 endocytosis through interaction with the auxin pathway. In contrast, mutations of ASA1 and the TIR1/AFBs auxin receptor genes enhance, rather than impair, the reduction effect of 50 μM MeJA on the plasma membrane accumulation of PIN2, suggesting that this action of jasmonate is independent of the auxin pathway. In addition to the MeJA effects on PIN2 endocytosis and plasma membrane residence, we also show that MeJA alters lateral auxin redistribution on gravi-stimulation, and therefore impairs the root gravitropic response. Our results highlight the importance of jasmonate-auxin interaction in the coordination of plant growth and the adaptation response.
    New Phytologist 04/2011; 191(2):360 - 375. DOI:10.1111/j.1469-8137.2011.03713.x
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    ABSTRACT: Recent identification of the Arabidopsis thaliana tyrosylprotein sulfotransferase (TPST) and a group of Tyr-sulfated peptides known as root meristem growth factors (RGFs) highlights the importance of protein Tyr sulfation in plant growth and development. Here, we report the action mechanism of TPST in maintenance of the root stem cell niche, which in the Arabidopsis root meristem is an area of four mitotically inactive quiescent cells plus the surrounding mitotically active stem cells. Mutation of TPST leads to defective maintenance of the root stem cell niche, decreased meristematic activity, and stunted root growth. We show that TPST expression is positively regulated by auxin and that mutation of this gene affects auxin distribution by reducing local expression levels of several PIN genes and auxin biosynthetic genes in the stem cell niche region. We also show that mutation of TPST impairs basal- and auxin-induced expression of the PLETHORA (PLT) stem cell transcription factor genes and that overexpression of PLT2 rescues the root meristem defects of the loss-of-function mutant of TPST. Together, these results support that TPST acts to maintain root stem cell niche by regulating basal- and auxin-induced expression of PLT1 and PLT2. TPST-dependent sulfation of RGFs provides a link between auxin and PLTs in regulating root stem cell niche maintenance.
    The Plant Cell 11/2010; 22(11):3692-709. DOI:10.1105/tpc.110.075721
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    ABSTRACT: Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2010; 30(38):12777-86. DOI:10.1523/JNEUROSCI.1102-10.2010
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    ABSTRACT: Abstract Deposition of ubiquitinated protein aggregates is a hallmark of neurodegeneration in both acute neural injuries, such as stroke, and chronic conditions, such as Parkinson's disease, but the underlying mechanisms are poorly understood. In the present study, we examined the role of Zn2+ in ischemia-induced impairment of the ubiquitin-proteasome system in the CA1 region of rat hippocampus after transient global ischemia. We found that scavenging endogenous Zn2+ reduced ischemia-induced ubiquitin conjugation and free ubiquitin depletion. Furthermore, exposure to zinc chloride increased ubiquitination and inhibited proteasomal enzyme activity in cultured hippocampal neurons in a concentration- and time-dependent manner. Further studies of the underlying mechanisms showed that Zn(2+)-induced ubiquitination required p38 activation. These findings indicate that alterations in Zn2+ homeostasis impair the protein degradation pathway.
    Journal of Neurochemistry 09/2009; 111(5):1094-103. DOI:10.1111/j.1471-4159.2009.06401.x
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    ABSTRACT: Plant roots show an impressive degree of plasticity in adapting their branching patterns to ever-changing growth conditions. An important mechanism underlying this adaptation ability is the interaction between hormonal and developmental signals. Here, we analyze the interaction of jasmonate with auxin to regulate lateral root (LR) formation through characterization of an Arabidopsis thaliana mutant, jasmonate-induced defective lateral root1 (jdl1/asa1-1). We demonstrate that, whereas exogenous jasmonate promotes LR formation in wild-type plants, it represses LR formation in jdl1/asa1-1. JDL1 encodes the auxin biosynthetic gene ANTHRANILATE SYNTHASE alpha1 (ASA1), which is required for jasmonate-induced auxin biosynthesis. Jasmonate elevates local auxin accumulation in the basal meristem of wild-type roots but reduces local auxin accumulation in the basal meristem of mutant roots, suggesting that, in addition to activating ASA1-dependent auxin biosynthesis, jasmonate also affects auxin transport. Indeed, jasmonate modifies the expression of auxin transport genes in an ASA1-dependent manner. We further provide evidence showing that the action mechanism of jasmonate to regulate LR formation through ASA1 differs from that of ethylene. Our results highlight the importance of ASA1 in jasmonate-induced auxin biosynthesis and reveal a role for jasmonate in the attenuation of auxin transport in the root and the fine-tuning of local auxin distribution in the root basal meristem.
    The Plant Cell 06/2009; 21(5):1495-511. DOI:10.1105/tpc.108.064303
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    ABSTRACT: Activation of NMDA subtypes of glutamate receptors is implicated in cell damage induced by ischemia as well as for the establishment of ischemic tolerance after ischemic preconditioning in animal models. We investigated the contributions of NR2A- and NR2B-containing NMDA receptors to ischemic cell death and ischemic tolerance in a rat model of transient global ischemia. Transient global ischemia was produced in rats by 4-vessel occlusion. Neuronal injury was analyzed by Fluoro-Jade B and Nissl staining. Phosphorylation of CREB was detected by Western blotting and immunohistochemistry. In situ hybridization and reverse transcriptase-polymerase chain reaction were used to evaluate the mRNA level of cpg15 and bdnf. NR2A subtype-specific antagonist NVP-AAM077 enhanced neuronal death after transient global ischemia and abolished the induction of ischemic tolerance. In contrast, NR2B subtype-specific antagonist ifenprodil attenuated ischemic cell death and enhanced preconditioning-induced neuroprotection. Furthermore, selectively blocking NR2A-, but not NR2B-, containing NMDA receptors inhibited ischemia-induced phosphorylation of CREB and the subsequent upregulation of CREB target genes such as cpg15 and bdnf. We found that NR2A- and NR2B-containing NMDA receptor subtypes play differential roles in ischemic neuronal death and ischemic tolerance, suggesting attractive new strategies for the development of drugs for patients with stroke.
    Stroke 09/2008; 39(11):3042-8. DOI:10.1161/STROKEAHA.108.521898
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    ABSTRACT: It is known that N-methyl-D-aspartate (NMDA) receptor in the basolateral nucleus of amygdala (BLA) is essential for fear memory formation. NMDA NR2B and NR2A subtype receptors exhibit difference in electrophysiological and signaling properties. However, it is unclear whether these two subtype receptors have different roles in fear memory formation. Here, we provide evidence, using pharmacological blockade and genetic interference, that NR2B is involved in acquisition of auditory fear memory in a conditioning-strength dependent way. Pre-conditioning intra-BLA infusion of the NR2B selective antagonist ifenprodil or Ro25-6981 impaired 48-h auditory fear memory (AFM) induced by five but not one CS-US pairing protocol, while similar treatment with the NR2A antagonist NVP-AAM077 disrupted memory for both protocols. Consistently, genetic over-expression of NR2B C-terminal in the BLA, which interferes with the C-terminal mediated intracellular signaling, produced a severe deficit in 48-h AFM for five but not one CS-US pairing protocol, whereas over-expression of NR2A C-terminal impaired memory for both protocols. Furthermore, pre-conditioning infusion of ifenprodil down-regulated the elevated phosphorylation level of extracellular signal-regulated kinase (ERK) induced by five CS-US pairing protocol. Thus, the involvement of BLA NR2B in AFM acquisition depends on conditioning strength.
    Neuropharmacology 09/2008; 55(2):238-46. DOI:10.1016/j.neuropharm.2008.05.030
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    ABSTRACT: The ability of synapses to undergo changes in structure and function in response to alterations of neuronal activity is an essential property of neural circuits. One way that this is achieved is through global changes in the molecular composition of the synapse; however, it is not clear how these changes are coupled to the dynamics of neuronal activity. Here we found that, in cultured rat cortical neurons, bidirectional changes of neuronal activity led to corresponding alterations in the expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of its receptor tropomyosin-related kinase B (TrkB), as well as in the level of synaptic proteins. Exogenous BDNF reversed changes in synaptic proteins induced by chronic activity blockade, while inhibiting Trk kinase activity or depleting endogenous BDNF abolished the concentration changes induced by chronic activity elevation. Both tetrodotoxin and bicuculline had significant, but opposite, effects on synaptic protein ubiquitination in a time-dependent manner. Furthermore, exogenous BDNF was sufficient to increase ubiquitination of synaptic proteins, whereas scavenging endogenous BDNF or inhibiting Trk kinase activity prevented the ubiquitination of synaptic proteins induced by chronic elevation of neuronal activity. Inhibiting the proteasome or blocking protein polyubiquitination mimicked the effect of tetrodotoxin on the levels of synaptic proteins and canceled the effects of BDNF. Our study indicates that BDNF-TrkB signaling acts upstream of the ubiquitin proteasome system, linking neuronal activity to protein turnover at the synapse.
    Journal of Biological Chemistry 08/2008; 283(30):21242-50. DOI:10.1074/jbc.M800282200
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    ABSTRACT: The size and shape of the plant leaf is an important agronomic trait. To understand the molecular mechanism governing plant leaf shape, we characterized a classic rice (Oryza sativa) dwarf mutant named narrow leaf1 (nal1), which exhibits a characteristic phenotype of narrow leaves. In accordance with reduced leaf blade width, leaves of nal1 contain a decreased number of longitudinal veins. Anatomical investigations revealed that the culms of nal1 also show a defective vascular system, in which the number and distribution pattern of vascular bundles are altered. Map-based cloning and genetic complementation analyses demonstrated that Nal1 encodes a plant-specific protein with unknown biochemical function. We provide evidence showing that Nal1 is richly expressed in vascular tissues and that mutation of this gene leads to significantly reduced polar auxin transport capacity. These results indicate that Nal1 affects polar auxin transport as well as the vascular patterns of rice plants and plays an important role in the control of lateral leaf growth.
    Plant physiology 07/2008; 147(4):1947-59. DOI:10.1104/pp.108.118778
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    ABSTRACT: Endocytosis of Trk (tropomyosin-related kinase) receptors is critical for neurotrophin signal transduction and biological functions. However, the mechanism governing endocytosis of TrkB (tropomyosin-related kinase B) and the specific contributions of TrkB endocytosis to downstream signaling are unknown. In this study, we report that blocking clathrin, dynamin, or AP2 in cultured neurons of the central nervous system inhibited brain-derived neurotrophic factor (BDNF)-induced activation of Akt but not ERK. Treating neurons with the clathrin inhibitor monodansylcadaverine or a peptide that blocks dynamin function specifically abrogated Akt pathway activation in response to BDNF but did not affect the response of other downstream effectors or the up-regulation of immediate early genes neuropeptide Y and activity-regulated cytoskeleton-associated protein. Similar effects were found in neurons expressing small interfering RNA to silence AP2 or a dominant negative form of dynamin that inhibits clathrin-mediated endocytosis. In PC12 cells, ERK but not Akt activation required TrkA endocytosis following stimulation with nerve growth factor, whereas the opposite was true when TrkA-expressing neurons were stimulated with nerve growth factor in the central nervous system. Thus, the specific effects of internalized Trk receptors probably depend on the presence of cell type-specific modulators of neurotrophin signaling and not on differences inherent to Trk receptors themselves. Endocytosis-dependent activation of Akt in neurons was found to be critical for BDNF-supported survival and dendrite outgrowth. Together, these results demonstrate the functional requirement of clathrin- and dynamin-dependent endocytosis in generating the full intracellular response of neurons to BDNF in the central nervous system.
    Journal of Biological Chemistry 06/2008; 283(19):13280-8. DOI:10.1074/jbc.M709930200
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    ABSTRACT: Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of synaptic connections and refinement of neuronal circuits, which may underlie learning and memory and contribute to pathogenesis of a diversity of neurological diseases, including epilepsy. Here, we found that NR2A and NR2B subunit-containing NMDARs were coupled to distinct intracellular signaling, resulting in differential BDNF expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Selective activation of NR2A-containing NMDARs increased BDNF gene expression. Activation of NR2B-containing NMDARs led to ERK1/2 phosphorylation. Furthermore, selectively blocking NR2A-containing NMDARs impaired epileptogenesis and the development of mossy fiber sprouting in the kindling and pilocarpine rat models of limbic epilepsy, whereas inhibiting NR2B-containing NMDARs had no effects in epileptogenesis and mossy fiber sprouting. Interestingly, blocking either NR2A- or NR2B-containing NMDARs decreased status epilepticus-induced neuronal cell death. The specific requirement of NR2A and its downstream signaling for epileptogenesis implicates attractive new targets for the development of drugs that prevent epilepsy in patients with brain injury.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 02/2007; 27(3):542-52. DOI:10.1523/JNEUROSCI.3607-06.2007
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    ABSTRACT: Late-phase long-term potentiation (L-LTP) and long-term memory depend on the transcription of mRNA of CRE-driven genes and synthesis of proteins. However, how synaptic signals propagate to the nucleus is unclear. Here we report that the CREB coactivator TORC1 (transducer of regulated CREB activity 1) undergoes neuronal activity-induced translocation from the cytoplasm to the nucleus, a process required for CRE-dependent gene expression and L-LTP. Overexpressing a dominant-negative form of TORC1 or down-regulating TORC1 expression prevented activity-dependent transcription of CREB target genes in cultured hippocampal neurons, while overexpressing a wild-type form of TORC1 facilitated basal and activity-induced transcription of CREB target genes. Furthermore, overexpressing the dominant-negative form of TORC1 suppressed the maintenance of L-LTP without affecting early-phase LTP, while overexpressing the wild-type form of TORC1 facilitated the induction of L-LTP in hippocampal slices. Our results indicate that TORC1 is essential for CRE-driven gene expression and maintenance of long-term synaptic potentiation.
    PLoS ONE 02/2006; 1(1):e16. DOI:10.1371/journal.pone.0000016
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Publication Stats

645 Citations
103.42 Total Impact Points

Institutions

  • 2014
    • East China University of Science and Technology
      • School of Pharmacy
      Shanghai, Shanghai Shi, China
  • 2009–2013
    • Chinese Academy of Sciences
      • • State Key Laboratory of Plant Genomics
      • • Institute of Neuroscience
      • • Graduate School
      Peping, Beijing, China
  • 2006–2009
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China
  • 2008
    • Fudan University
      • State Key Laboratory of Medical Neurobiology
      Shanghai, Shanghai Shi, China