CoChat
Sign Up
Cited by 74Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingGenetics and Neurodevelopmental Disorders

Neuronal Rho GEFs in Synaptic Physiology and Behavior

Open access
Miller, Megan B., Yan, Yan, Eipper, Betty A., Mains, Richard E.·2013·The Neuroscientist
DOI 10.1177/1073858413475486PMC PMC3927235
Open this paper in CoChat — free account

Abstract

In the mammalian brain, the majority of excitatory synapses are housed in micron-sized dendritic protrusions called spines, which can undergo rapid changes in shape and number in response to increased or decreased synaptic activity. These dynamic alterations in dendritic spines require precise control of the actin cytoskeleton. Within spines, multidomain Rho guanine nucleotide exchange factors (Rho GEFs) coordinate activation of their target Rho GTPases by a variety of pathways. In this review, we focus on the handful of disease-related Rho GEFs (Kalirin; Trio; Tiam1; P-Rex1,2; RasGRF1,2; Collybistin) localized at synapses and known to affect electrophysiology, spine morphology, and animal behavior. The goal is to integrate structure/function studies with measurements of synaptic function and behavioral phenotypes in animal models.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1177/1073858413475486

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • RhoGEFs kalirin-7, Trio, and Tiam are expressed in spines and phosphorylated by CaMKII.

    “The RhoGEFs that have received the most attention are kalirin-7, Trio, and Tiam, which are all expressed in spines and phosphorylated by CaMKII (314–317).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [316]

    In “Discovery and expression” (page unavailable), the review places Kal7 in dendritic spines; “Protein structure and signaling” says CaMKII is among the kinases that target Kalirin. The Tiam1 “Electrophysiology and synaptic function” section places Tiam1 in spines and reports calcium-dependent phosphorylation, but does not identify CaMKII as the kinase. The cited passages do not establish that Trio is expressed in spines or phosphorylated by CaMKII, so the claim that all three share both properties is not supported. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 121 · Cited by 74

Research works printed but not linked: 119

  1. Abe H Okazawa M Nakanishi S Gene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells Proc Natl Acad Sci U S A 2012 109 8734 8739 22586091 PMC3365191
  2. Alam MR Caldwell BD Johnson RC Darlington DN Mains RE Eipper BA Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme J Biol Chem 1996 271 28636 28640 8910496
  3. Astigarraga S Hofmeyer K Farajian R Treisman JE Three Drosophila liprins interact to control synapse formation J Neurosci 2010 30 15358 15368 21084592 PMC2999520
  4. Awasaki T Saito M Sone M Suzuki E Sakai R Ito K The Drosophila trio plays an essential role in patterning of axons by regulating their directional extension Neuron 2000 26 119 131 10798397
  5. Balamatsias D Kong AM Waters JE Sriratana A Gurung R Bailey CG Identification of P-Rex1 as a novel Rac1-guanine nucleotide exchange factor (GEF) that promotes actin remodeling and GLUT4 protein trafficking in adipocytes J Biol Chem 2011 286 43229 43240 22002247 PMC3234845
  6. Ball RW Warren-Paquin M Tsurudome K Liao EH Elazzouzi F Cavanagh C Retrograde BMP signaling controls synaptic growth at the NMJ by regulating trio expression in motor neurons Neuron 2010 66 536 549 20510858
  7. Baouz S Jacquet E Bernardi A Parmeggiani A The N-terminal moiety of CDC25(Mm), a GDP/GTP exchange factor of Ras proteins, controls the activity of the catalytic domain. Modulation by calmodulin and calpain J Biol Chem 1997 272 6671 6676 9045698
  8. Bateman J Shu H Van Vactor D The guanine nucleotide exchange factor trio mediates axonal development in the Drosophila embryo Neuron 2000 26 93 106 10798395
  9. Bouquier N Vignal E Charrasse S Weill M Schmidt S Leonetti JP A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway Chem Biol 2009 16 657 666 19549603
  10. Brambilla R Gnesutta N Minichiello L White G Roylance AJ Herron CE A role for the Ras signalling pathway in synaptic transmission and long-term memory Nature 1997 390 281 286 9384379
  11. Briancon-Marjollet A Ghogha A Nawabi H Triki I Auziol C Fromont S Trio mediates netrin-1-induced Rac1 activation in axon outgrowth and guidance Mol Cell Biol 2008 28 2314 2323 18212043 PMC2268419
  12. Cahill ME Xie Z Day M Photowala H Barbolina MV Miller CA Penzes P Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes Proc Natl Acad Sci U S A 2009 106 13058 13063 19625617 PMC2722269
  13. Chan JP Hu Z Sieburth D Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release Genes Dev 2012 26 1070 1085 22588719 PMC3360562
  14. Chen L Zhang LJ Greer P Tung PS Moran MF A murine CDC25/ras-GRF-related protein implicated in Ras regulation Dev Genet 1993 14 339 346 8293576
  15. Chiou TT Bonhomme B Jin H Miralles CP Xiao H Fu Z Differential regulation of the postsynaptic clustering of gamma-aminobutyric acid type A (GABAA) receptors by collybistin isoforms J Biol Chem 2011 286 22456 22468 21540179 PMC3121391
  16. Chiu CY Leng S Martin KA Kim E Gorman S Duhl DM Cloning and characterization of T-cell lymphoma invasion and metastasis 2 (TIAM2), a novel guanine nucleotide exchange factor related to TIAM1 Genomics 1999 61 66 73 10512681
  17. d'Isa R Clapcote SJ Voikar V Wolfer DP Giese KP Brambilla R Mice Lacking Ras-GRF1 Show Contextual Fear Conditioning but not Spatial Memory Impairments: Convergent Evidence from Two Independently Generated Mouse Mutant Lines Front Behav Neurosci 2011 5 78 22164138 PMC3230787
  18. de Hoog CL Fan WT Goldstein MD Moran MF Koch CA Calmodulin-independent coordination of Ras and extracellular signal-regulated kinase activation by Ras-GRF2 Mol Cell Biol 2000 20 2727 2733 10733575 PMC85488
  19. Debant A Serra-Pages C Seipel K O'Brien S Tang M Park SH Streuli M The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains Proc Natl Acad Sci U S A 1996 93 5466 5471 8643598 PMC39269
  20. Donald S Hill K Lecureuil C Barnouin R Krugmann S Coadwell JW P-Rex2, a new guanine-nucleotide exchange factor for Rac FEBS Lett 2004 572 172 176 15304343
  21. Donald S Humby T Fyfe I Segonds-Pichon A Walker SA Andrews SR P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination Proc Natl Acad Sci U S A 2008 105 4483 4488 18334636 PMC2393786
  22. Ehler E van Leeuwen F Collard JG Salinas PC Expression of Tiam-1 in the developing brain suggests a role for the Tiam-1-Rac signaling pathway in cell migration and neurite outgrowth Mol Cell Neurosci 1997 9 1 12 9204476
  23. Farnsworth CL Freshney NW Rosen LB Ghosh A Greenberg ME Feig LA Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF Nature 1995 376 524 527 7637786
  24. Fasano S Bezard E D'Antoni A Francardo V Indrigo M Qin L Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with L-dopa-induced dyskinesia Proc Natl Acad Sci U S A 2010 107 21824 21829 21115823 PMC3003069
  25. Fasano S D'Antoni A Orban PC Valjent E Putignano E Vara H Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) controls activation of extracellular signal-regulated kinase (ERK) signaling in the striatum and long-term behavioral responses to cocaine Biol Psychiatry 2009 66 758 768 19446794 PMC2910545
  26. Feig LA Regulation of Neuronal Function by Ras-GRF Exchange Factors Genes Cancer 2011 2 306 319 21779501 PMC3128633
  27. Fernandez-Medarde A Barhoum R Riquelme R Porteros A Nunez A de Luis A RasGRF1 disruption causes retinal photoreception defects and associated transcriptomic alterations J Neurochem 2009 110 641 652 19457086
  28. Fernandez-Medarde A Esteban LM Nunez A Porteros A Tessarollo L Santos E Targeted disruption of Ras-Grf2 shows its dispensability for mouse growth and development Mol Cell Biol 2002 22 2498 2504 11909944 PMC133706
  29. Fernandez-Medarde A Santos E The RasGrf family of mammalian guanine nucleotide exchange factors Biochim Biophys Acta 2011 1815 170 188 21111786
  30. Gerard A van der Kammen RA Janssen H Ellenbroek SI Collard JG The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration Blood 2009 113 6138 6147 19139083
  31. Giese KP Friedman E Telliez JB Fedorov NB Wines M Feig LA Hippocampus-dependent learning and memory is impaired in mice lacking the Ras-guanine-nucleotide releasing factor 1 (Ras-GRF1) Neuropharmacology 2001 41 791 800 11640934
  32. Goto A Hoshino M Matsuda M Nakamura T Phosphorylation of STEF/Tiam2 by protein kinase A is critical for Rac1 activation and neurite outgrowth in dibutyryl cAMP-treated PC12D cells Mol Biol Cell 2011 22 1780 1790 21460187 PMC3093328
  33. Habets GG Scholtes EH Zuydgeest D van der Kammen RA Stam JC Berns A Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins Cell 1994 77 537 549 7999144
  34. Hansel DE Quinones ME Ronnett GV Eipper BA Kalirin, a GDP/GTP exchange factor of the Dbl family, is localized to nerve, muscle, and endocrine tissue during embryonic rat development J Histochem Cytochem 2001 49 833 844 11410608
  35. Harvey K Duguid IC Alldred MJ Beatty SE Ward H Keep NH The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering J Neurosci 2004 24 5816 5826 15215304 PMC6729214
  36. Hernandez-Negrete I Carretero-Ortega J Rosenfeldt H Hernandez-Garcia R Calderon-Salinas JV Reyes-Cruz G P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration J Biol Chem 2007 282 23708 23715 17565979
  37. Hill K Krugmann S Andrews SR Coadwell WJ Finan P Welch HC Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits J Biol Chem 2005 280 4166 4173 15545267
  38. Hoshino M Sone M Fukata M Kuroda S Kaibuchi K Nabeshima Y Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1 J Biol Chem 1999 274 17837 17844 10364228
  39. Jackson C Welch HC Bellamy TC Control of cerebellar long-term potentiation by P-Rex-family guanine-nucleotide exchange factors and phosphoinositide 3-kinase PLoS One 2010 5 e11962 20694145 PMC2915919
  40. Jedlicka P Papadopoulos T Deller T Betz H Schwarzacher SW Increased network excitability and impaired induction of long-term potentiation in the dentate gyrus of collybistin-deficient mice in vivo Mol Cell Neurosci 2009 41 94 100 19236916
  41. Kawauchi T Chihama K Nabeshima Y Hoshino M The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration EMBO J 2003 22 4190 4201 12912917 PMC175802
  42. Kins S Betz H Kirsch J Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin Nat Neurosci 2000 3 22 29 10607391
  43. Kiraly DD Eipper-Mains JE Mains RE Eipper BA Synaptic plasticity, a symphony in GEF ACS Chem Neurosci 2010a 1 348 365 20543890 PMC2882301
  44. Kiraly DD Lemtiri-Chlieh F Levine ES Mains RE Eipper BA Kalirin binds the NR2B subunit of the NMDA receptor, altering its synaptic localization and function J Neurosci 2011a 31 12554 12565 21880917 PMC3172699
  45. Kiraly DD Ma XM Mazzone CM Xin X Mains RE Eipper BA Behavioral and morphological responses to cocaine require kalirin7 Biol Psychiatry 2010b 68 249 255 20452575 PMC2907465
  46. Kiraly DD Stone KL Colangelo CM Abbott T Wang Y Mains RE Eipper BA Identification of Kalirin-7 as a potential post-synaptic density signaling hub J Proteome Res 2011b 10 2828 2841 21488700 PMC3107868
  47. Kneussel M Engelkamp D Betz H Distribution of transcripts for the brain-specific GDP/GTP exchange factor collybistin in the developing mouse brain Eur J Neurosci 2001 13 487 492 11168555
  48. Krapivinsky G Krapivinsky L Manasian Y Ivanov A Tyzio R Pellegrino C The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1 Neuron 2003 40 775 784 14622581
  49. Kunda P Paglini G Quiroga S Kosik K Caceres A Evidence for the involvement of Tiam1 in axon formation J Neurosci 2001 21 2361 2372 11264310 PMC6762399
  50. Kushima I Nakamura Y Aleksic B Ikeda M Ito Y Shiino T Resequencing and association analysis of the KALRN and EPHB1 genes and their contribution to schizophrenia susceptibility Schizophr Bull 2012 38 552 560 21041834 PMC3329972
  51. Lai KO Wong AS Cheung MC Xu P Liang Z Lok KC TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory Nat Neurosci 2012 15 1506 1515 23064382 PMC7511999
  52. Lemtiri-Chlieh F Zhao L Kiraly DD Eipper BA Mains RE Levine ES Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity BMC Neurosci 2011 12 126 22182308 PMC3261125
  53. Li S Tian X Hartley DM Feig LA Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression J Neurosci 2006 26 1721 1729 16467520 PMC6793631
  54. Li W Li QJ An SC Preventive effect of estrogen on depression-like behavior induced by chronic restraint stress Neurosci Bull 2010 26 140 146 20332819 PMC5560369
  55. Liebl EC Forsthoefel DJ Franco LS Sample SH Hess JE Cowger JA Dosage-sensitive, reciprocal genetic interactions between the Abl tyrosine kinase and the putative GEF trio reveal trio's role in axon pathfinding Neuron 2000 26 107 118 10798396
  56. Luo L Trio quartet in D. (melanogaster) Neuron 2000 26 1 2 10798384
  57. Lutz S Shankaranarayanan A Coco C Ridilla M Nance MR Vettel C Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs Science 2007 318 1923 1927 18096806
  58. Ma QL Yang F Calon F Ubeda OJ Hansen JE Weisbart RH p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesis J Biol Chem 2008a 283 14132 14143 18347024 PMC2376243
  59. Ma XM Huang JP Eipper BA Mains RE Expression of Trio, a member of the Dbl family of Rho GEFs in the developing rat brain J Comp Neurol 2005 482 333 348 15669055
  60. Ma XM Huang JP Xin X Yan Y Mains RE Eipper BA A role for kalirin in the response of rat medium spiny neurons to cocaine Mol Pharmacol 2012 82 738 745 22828798 PMC3463218
  61. Ma XM Johnson RC Mains RE Eipper BA Expression of kalirin, a neuronal GDP/GTP exchange factor of the trio family, in the central nervous system of the adult rat J Comp Neurol 2001 429 388 402 11116227
  62. Ma XM Kiraly DD Gaier ED Wang Y Kim EJ Levine ES Eipper BA Mains RE Kalirin-7 is required for synaptic structure and function J Neurosci 2008b 28 12368 12382 19020030 PMC2586970
  63. Ma XM Wang Y Ferraro F Mains RE Eipper BA Kalirin-7 is an essential component of both shaft and spine excitatory synapses in hippocampal interneurons J Neurosci 2008c 28 711 724 18199770 PMC2570025
  64. Mains RE Kiraly DD Eipper-Mains JE Ma XM Eipper BA Kalrn promoter usage and isoform expression respond to chronic cocaine exposure BMC Neurosci 2011 12 20 21329509 PMC3048553
  65. Malliri A van der Kammen RA Clark K van der Valk M Michiels F Collard JG Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours Nature 2002 417 867 871 12075356
  66. Mandela P Ma XM Kalirin, a key player in synapse formation, is implicated in human diseases Neural Plast 2012 2012 728161 22548195 PMC3324156
  67. Mandela P Yankova M Conti LH Ma X Grady J Eipper BA Mains RE Kalrn plays key roles within and outside of the nervous system BMC Neurosci 2012 13 136 23116210 PMC3541206
  68. Matsuo N Terao M Nabeshima Y Hoshino M Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology Mol Cell Neurosci 2003 24 69 81 14550769
  69. Mattingly RR Phosphorylation of serine 916 of Ras-GRF1 contributes to the activation of exchange factor activity by muscarinic receptors J Biol Chem 1999 274 37379 37384 10601308
  70. Mattingly RR Macara IG Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein beta gamma subunits Nature 1996 382 268 272 8717044
  71. May V Schiller MR Eipper BA Mains RE Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms J Neurosci 2002 22 6980 6990 12177196 PMC6757900
  72. Mayeenuddin LH McIntire WE Garrison JC Differential sensitivity of P-Rex1 to isoforms of G protein betagamma dimers J Biol Chem 2006 281 1913 1920 16301321
  73. McMullan R Anderson A Nurrish S Behavioral and immune responses to infection require Galphaq-RhoA signaling in C. elegans PLoS Pathog 2012 8 e1002530 22359503 PMC3280986
  74. McPherson CE Eipper BA Mains RE Genomic organization and differential expression of Kalirin isoforms Gene 2002 284 41 51 11891045
  75. McPherson CE Eipper BA Mains RE Multiple novel isoforms of Trio are expressed in the developing rat brain Gene 2005 347 125 135 15715966
  76. Mendoza-Naranjo A Gonzalez-Billault C Maccioni RB Abeta1–42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases J Cell Sci 2007 120 279 288 17200137
  77. Michiels F Habets GG Stam JC van der Kammen RA Collard JG A role for Rac in Tiam1-induced membrane ruffling and invasion Nature 1995 375 338 340 7753201
  78. Miyamoto Y Yamauchi J Tanoue A Wu C Mobley WC TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology Proc Natl Acad Sci U S A 2006 103 10444 10449 16801538 PMC1502477
  79. Montenegro-Venegas C Tortosa E Rosso S Peretti D Bollati F Bisbal M MAP1B regulates axonal development by modulating Rho-GTPase Rac1 activity Mol Biol Cell 2010 21 3518 3528 20719958 PMC2954117
  80. Norum JH Methi T Mattingly RR Levy FO Endogenous expression and protein kinase A-dependent phosphorylation of the guanine nucleotide exchange factor Ras-GRF1 in human embryonic kidney 293 cells FEBS J 2005 272 2304 2316 15853814
  81. O'Brien SP Seipel K Medley QG Bronson R Segal R Streuli M Skeletal muscle deformity and neuronal disorder in Trio exchange factor-deficient mouse embryos Proc Natl Acad Sci U S A 2000 97 12074 12078 11050238 PMC17296
  82. Papadopoulos T Korte M Eulenburg V Kubota H Retiounskaia M Harvey RJ Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice EMBO J 2007 26 3888 3899 17690689 PMC1994120
  83. Parelkar NK Jiang Q Chu XP Guo ML Mao LM Wang JQ Amphetamine alters Ras-guanine nucleotide-releasing factor expression in the rat striatum in vivo Eur J Pharmacol 2009 619 50 56 19686726 PMC2757775
  84. Patrizi A Viltono L Frola E Harvey K Harvey RJ Sassoe-Pognetto M Selective localization of Collybistin at a subset of inhibitory synapses in brain circuits J Comp Neurol 2012 520 130 141 21681748
  85. Peng YJ He WQ Tang J Tao T Chen C Gao YQ Trio is a key guanine nucleotide exchange factor coordinating regulation of the migration and morphogenesis of granule cells in the developing cerebellum J Biol Chem 2010 285 24834 24844 20516067 PMC2915719
  86. Penzes P Cahill ME Jones KA VanLeeuwen JE Woolfrey KM Dendritic spine pathology in neuropsychiatric disorders Nat Neurosci 2011 14 285 293 21346746 PMC3530413
  87. Penzes P Jones KA Dendritic spine dynamics--a key role for kalirin-7 Trends Neurosci 2008 31 419 427 18597863 PMC3973420
  88. Rabiner CA Mains RE Eipper BA Kalirin: a dual Rho guanine nucleotide exchange factor that is so much more than the sum of its many parts Neuroscientist 2005 11 148 160 15746383
  89. Rojas RJ Yohe ME Gershburg S Kawano T Kozasa T Sondek J Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain J Biol Chem 2007 282 29201 29210 17606614 PMC2655113
  90. Rossman KL Der CJ Sondek J GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors Nat Rev Mol Cell Biol 2005 6 167 180 15688002
  91. Rubino T Forlani G Vigano D Zippel R Parolaro D Ras/ERK signalling in cannabinoid tolerance: from behaviour to cellular aspects J Neurochem 2005 93 984 991 15857401
  92. Rubino T Vigano D Premoli F Castiglioni C Bianchessi S Zippel R Changes in the expression of G protein-coupled receptor kinases and beta-arrestins in mouse brain during cannabinoid tolerance: a role for RAS-ERK cascade Mol Neurobiol 2006 33 199 213 16954596
  93. Schiller MR Coupling receptor tyrosine kinases to Rho GTPases--GEFs what's the link Cell Signal 2006 18 1834 1843 16725310
  94. Schiller MR Ferraro F Wang Y Ma XM McPherson CE Sobota JA Mains RE Eipper BA Autonomous functions for the Sec14p/spectrin-repeat region of Kalirin Exp Cell Res 2008 314 2674 2691 18585704 PMC2613971
  95. Shimojima K Sugawara M Shichiji M Mukaida S Takayama R Imai K Yamamoto T Loss of function mutation of collybistin is responsible for X-linked mental retardation associated with epilepsy J Hum Genet 2011 56 561 565 21633362
  96. Terawaki S Kitano K Mori T Zhai Y Higuchi Y Itoh N The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module EMBO J 2010 29 236 250 19893486 PMC2775898
  97. Tian X Feig LA Age-dependent participation of Ras-GRF proteins in coupling calcium-permeable AMPA glutamate receptors to Ras/Erk signaling in cortical neurons J Biol Chem 2006 281 7578 7582 16407208
  98. Tolias KF Bikoff JB Burette A Paradis S Harrar D Tavazoie S The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines Neuron 2005 45 525 538 15721239
  99. Tolias KF Bikoff JB Kane CG Tolias CS Hu L Greenberg ME The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development Proc Natl Acad Sci U S A 2007 104 7265 7270 17440041 PMC1855368
  100. Tolias KF Duman JG Um K Control of synapse development and plasticity by Rho GTPase regulatory proteins Prog Neurobiol 2011 94 133 148 21530608 PMC3129138
  101. Tonini R Franceschetti S Parolaro D Sala M Mancinelli E Tininini S Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability Mol Cell Neurosci 2001 18 691 701 11749043
  102. Tyagarajan SK Ghosh H Harvey K Fritschy JM Collybistin splice variants differentially interact with gephyrin and Cdc42 to regulate gephyrin clustering at GABAergic synapses J Cell Sci 2011 124 2786 2796 21807943 PMC3148131
  103. Urano D Nakata A Mizuno N Tago K Itoh H Domain-domain interaction of P-Rex1 is essential for the activation and inhibition by G protein betagamma subunits and PKA Cell Signal 2008 20 1545 1554 18514484
  104. Vigil D Cherfils J Rossman KL Der CJ Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer 2010 10 842 857 21102635 PMC3124093
  105. Wang L Hauser ER Shah SH Pericak-Vance MA Haynes C Crosslin D Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease Am J Hum Genet 2007 80 650 663 17357071 PMC1852708
  106. Waters JE Astle MV Ooms LM Balamatsias D Gurung R Mitchell CA P-Rex1 - a multidomain protein that regulates neurite differentiation J Cell Sci 2008 121 2892 2903 18697831
  107. Welch HC Coadwell WJ Ellson CD Ferguson GJ Andrews SR Erdjument-Bromage H P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac Cell 2002 108 809 821 11955434
  108. Welch HC Condliffe AM Milne LJ Ferguson GJ Hill K Webb LM P-Rex1 regulates neutrophil function Curr Biol 2005 15 1867 1873 16243035
  109. Williams SL Lutz S Charlie NK Vettel C Ailion M Coco C Trio's Rho-specific GEF domain is the missing Galpha q effector in C. elegans Genes Dev 2007 21 2731 2746 17942708 PMC2045128
  110. Woodcock SA Rushton HJ Castaneda-Saucedo E Myant K White GR Blyth K Tiam1-Rac signaling counteracts Eg5 during bipolar spindle assembly to facilitate chromosome congression Curr Biol 2010 20 669 675 20346677 PMC2989435
  111. Wu JH Fanaroff AC Sharma KC Zhang L Smith LS Brian L Eipper BA Mains RE Freedman NJ Kalirin Promotes Neointimal Hyperplasia by Activating Rac in Smooth Muscle Cells Arterioscler Thromb Vasc Biol 2012 In press PMC3638886 23288169
  112. Xie Z Cahill ME Radulovic J Wang J Campbell SL Miller CA Hippocampal phenotypes in kalirin-deficient mice Mol Cell Neurosci 2011 46 45 54 20708080 PMC3576140
  113. Xin X Rabiner CA Mains RE Eipper BA Kalirin12 interacts with dynamin BMC Neurosci 2009 10 61 19534784 PMC2703648
  114. Yang H Cooley D Legakis JE Ge Q Andrade R Mattingly RR Phosphorylation of the Ras-GRF1 exchange factor at Ser916/898 reveals activation of Ras signaling in the cerebral cortex J Biol Chem 2003 278 13278 13285 12538592
  115. Yoo S Kim Y Lee H Park S Park S A gene trap knockout of the Tiam-1 protein results in malformation of the early embryonic brain Mol Cells 2012 34 103 108 22661025 PMC3887777
  116. Yoshizawa M Kawauchi T Sone M Nishimura YV Terao M Chihama K Involvement of a Rac activator,P-Rex1, in neurotrophin-derived signaling and neuronal migration J Neurosci 2005 25 4406 4419 15858067 PMC6725123
  117. Youn H Jeoung M Koo Y Ji H Markesbery WR Ji I Kalirin is under-expressed in Alzheimer's disease hippocampus J Alzheimers Dis 2007 11 385 397 17851188
  118. Zhang GC Hoffmann J Parelkar NK Liu XY Mao LM Fibuch EE Cocaine increases Ras-guanine nucleotide-releasing factor 1 protein expression in the rat striatum in vivo Neurosci Lett 2007 427 117 121 17931779
  119. Zhang H Macara IG The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis Nat Cell Biol 2006 8 227 237 16474385

Authors
Miller, M. B., Yan, Y., Eipper, B. A., & Mains, R. E.
Affiliations
UConn Health (US)
Corresponding author
Mains, Richard E.
ORCID
Venue
The Neuroscientist
Publisher
SAGE Publications
Published
2013-02-11
Volume
19
Issue
3
Pages
255-273
ISSN
  • 1073-8584 (ISSN-L)
  • 1089-4098
DOI
10.1177/1073858413475486
PMC
PMC3927235
OpenAlex
W2119442942
Cited by
74
References
121
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 7 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 1
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • The Neuroscientist (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Drug Abuse (R21DA018274, R01DA023082, DA-23082)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-32948, R01DK032948, DK32949, R01DK032949, R56DK032949, R37DK032949, R56DK032948)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
RhoGEF, dendritic spines, synaptic plasticity, actin cytoskeleton, Rho GTPases, Kalirin, trios, Tiam1, P-Rex1, RASGRF1, RASGRF2, collybistin, dendritic spine morphology, behavior, neurodevelopmental disorders
MeSH terms
Animals, Behavior, Brain, Humans, Neurons, Synapses, Signal Transduction, Dendritic Spines, Rho Guanine Nucleotide Exchange Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review