Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus

Synaptic NMDA-type glutamate receptors are anchored to the second of three PDZ (PSD-95/Discs large/ZO-1) domains in the postsynaptic density (PSD) protein PSD-95. Here, we report that citron, a protein target for the activated form of the small GTP-binding protein Rho, preferentially binds the third PDZ domain of PSD-95. In GABAergic neurons from the hippocampus, citron forms a complex with PSD-95 and is concentrated at the postsynaptic side of glutamatergic synapses. Citron is expressed only at low levels in glutamatergic neurons in the hippocampus and is not detectable at synapses onto these neurons. In contrast to citron, p135 SynGAP, an abundant synaptic Ras GTPase-activating protein that can bind to all three PDZ domains of PSD-95, and Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) are concentrated postsynaptically at glutamatergic synapses on glutamatergic neurons. CaM kinase II is not expressed and p135 SynGAP is expressed in less than half of hippocampal GABAergic neurons. Segregation of citron into inhibitory neurons does not occur in other brain regions. For example, citron is expressed at high levels in most thalamic neurons, which are primarily glutamatergic and contain CaM kinase II. In several other brain regions, citron is present in a subset of neurons that can be either GABAergic or glutamatergic and can sometimes express CaM kinase II. Thus, in the hippocampus, signal transduction complexes associated with postsynaptic NMDA receptors are different in glutamatergic and GABAergic neurons and are specialized in a way that is specific to the hippocampus

Friends of Musselman Library Newsletter Spring 2005

Table of Contents: From the Director: “Forever Free” Abraham Lincoln Exhibit (Robin Wagner, Christina Ericson Hansen ’92, Gabor Boritt); Fortenbaugh Internship Expands (Julia Grover ’06, Anne Kennedy ’05); Bontanicals Brighten Browsing Room (Jim Ramos); Asian Art Award Announced (Karen Drickamer); Apache Visions: Exhibit Features Skateboard Art; Barbara Holley Establishes Preservation Fund for Library (Barbara Holley ’54); Library News: Athletic Windfall, Reading Al Fresco, Library Tunes, Newspaper and Magazine Browsing, Majestic Theatre Exhibit, Civil War Manuscripts, Oral History, FoML Helps New Voters (Henry T. Bream ’24, Jack Bream ’57, Robert C. ’62, Marsha Parker ’62, Dr. William Sunderman Senior ’19, Jake Yingling ’52 and Genevieve Yingling); Student Projects Featured in Music Exhibition (Dr. William Sunderman Senior ’19, Tim Sestrick, Marta Robertson); In Her Own Words; Spring Lecture on Citron (Molly Hutton, Thomas Citron ’47, Virginia Eshbach Citron ’47); Second Spring Friends Lecture: “The Cyclorama Building and the Loss of Cultural Landscape at Gettysburg”; Focus on Philanthropy: Gift Supports Purchases of Nineteenth Century Documents (Dr. Bradley Hoch); Giving Students a Break (Meggan Emler Smith \u2704, Anne Kennedy, Sujita Kong); Spotlight on Collecting: Captivity Narritives (Edward Maharay, Janet Hancock Maharay ’39, Tim Shannon); Weird and Gross in the Librar

Citron kinase is an essential effector of the Pbl-activated Rho signalling pathway in Drosophila melanogaster.

Copyright © 2004 The Company of Biologists LtdPebble (Pbl)-activated RhoA signalling is essential for cytokinesis in Drosophila melanogaster. Here we report that the Drosophila citron gene encodes an essential effector kinase of Pbl-RhoA signalling in vivo. Drosophila citron is expressed in proliferating tissues but is downregulated in differentiating tissues. We find that Citron can bind RhoA and that localisation of Citron to the contractile ring is dependent on the cytokinesis-specific Pbl-RhoA signalling. Phenotypic analysis of mutants showed that citron is required for cytokinesis in every tissue examined, with mutant cells exhibiting multinucleate and hyperploid phenotypes. Strong genetic interactions were observed between citron and pbl alleles and constructs. Vertebrate studies implicate at least two Rho effector kinases, Citron and Rok, in cytokinesis. By contrast, we failed to find evidence for a role for the Drosophila ortholog of Rok in cell division. We conclude that Citron plays an essential, non-redundant role in the Rho signalling pathway during Drosophila cytokinesis.Tetyana Shandala, Stephen L. Gregory, Hazel E. Dalton, Masha Smallhorn and Robert Sain

Determinants Factor of the Captive Breeding Success of Citron-crested Cockatoo (Cacatua Sulphurea Citrinocristata, Fraser 1844)

Citron-crested cockatoo (Cacatua sulphurea citrinocristata) is one of endemic bird which endangered in Sumba islands and protected by in law. The study was aimed to analyze the determinants factor of the captive breeding success of citron-crested cockatoo. The research was conducted in January-March 2018, in Mega Bird and Orchid Farm Bogor, Ragunan Zoo, Rahardjo Bird Farm Solo, and Cikembulan Zoo. Determinant factor of the captive breeding success of citron-crested cockatoo were analyze using PCA with SPSS 22 software. The main components which are important factors for captive breeding success of Citron-crested cockatoo were breeding techniques (feed, time of handling, the number of productive parent and capital), condition of citron-crested cockatoo cage (temperature and humidity) and human resources (duration time of the breeding and knowledge of the keeper)

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development

Defective Neurogenesis in Citron Kinase Knockout Mice by Altered Cytokinesis and Massive Apoptosis

AbstractCitron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Citron-K−/− mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS

An Assessment of Mayor Bloomberg’s Public Health Legacy

As New York City Mayor Michael Bloomberg’s last term was coming to an end, Professor Gostin wrote an article for the Hasting Center Report addressing Bloomberg’s public health legacy. Rodger Citron has edited that article into a question and answer format and also asked Professor Gostin to elaborate on a number of points made in that article