The Challenges of Studying Leukocyte Trafficking into the CNS
Investigation of the molecular signals involved in immune cell migration into a given tissue requires both in vitro and in vivo approaches. When studying immune cell migration across the BBB, both approaches are difficult, and have their pitfalls. Maintenance of the unique characteristics of the BBB en-dothelium critically depends on the continuous molecular crosstalk with the CNS microenvironment. To date, the identity of the requisite molecules for maintaining BBB characteristics in CNS...
Synaptic Functions of Laminins
Laminins are trimeric molecules consisting of an alpha chain, a beta chain, and a gamma chain, arranged in a cross-like structure with their C-termini intercoiled. Mammals express at least five alpha chains, three beta chains and three gamma chains. Distinct genes encode each subunit, and the expression patterns are often dynamic during development. The laminins are known to act as ligands for integrins and other cell-surface receptors such as dystrogly-can. In the NMJ laminins are dynamically...
In Vivo Analysis of CD8 T Cell Priming and Tolerance Induction
The priming of CD8 T cells has been shown to require a short time of interaction with antigen-presenting cells followed by a long antigen-independent expansion process Kaech and Ahmed 2001 van Stipdonk et al. 2003 Wong and Pamer 2001 . As mentioned in the previous section, this is very different from the current understanding of antigen requirements for CD4 T cell expansion Iezzi et al. 1998 Obst et al. 2005 . However, induction of antigen-dependent tolerance of CD8 T cells appears to require...
MHC Expression and Antigen Presentation by Endothelial Cells
Microvascular endothelial cells from the human kidney Muczynski et al. 2003 , human heart McDougall et al. 1997 , skin Vora et al. 1994 , gut Har-aldsen et al. 1998 and liver Lohse et al. 1996 constitutively express MHC class II molecules. In general, most microvascular endothelial cells from humans show constitutive expression of MHC class II molecules, whereas most murine microvascular endothelial cells seem to require pro-inflammatory mediators in order to up-regulate expression of MHC class...
Developmental Assembly of the Active Zone The Active Zone Precursor Vesicle
During development, a previously undetermined region of axonal plasma membrane differentiates into a presynaptic active zone with a highly complex and organized molecular composition that warrants neurotransmitter release with high specificity and fidelity in precise alignment with the postsynaptic receptive apparatus. Our understanding of the molecular and cellular mechanism underlying this process is surprisingly vague compared with our knowledge about the presynaptic function. Synapse...
Molecular Organization of the Active Zone
Several CAZ-specific constituents have been identified and characterized at the molecular level, including the UNC13 Munc13 proteins, the Rab3-interacting molecules RIMs , Bassoon, Piccolo Aczonin and the ERC2 CAST Garner et al. 2000 Rosenmund et al. 2003 Ziv and Garner 2004 . These proteins are physically interconnected and thus thought to form the molecular Fig. 1 Molecular organization of the CAZ. The CAZ-specific proteins RIMs, Munc13s, Bassoon, Piccolo and CAST ERC are thought to localize...
New Model for Sustained Signaling Through the Immunological Synapse
Studies on the IS bring together three parallel lines of experimentation in immunology 1 signal transduction, 2 cell adhesion, and 3 directed secretion. TCR signaling is based on a tyrosine kinase cascade that leads to rapid activation of phospholipase C y Weiss and Littman 1994 . The key tyrosine kinases are Lck, which initiates phosphorylation of immunotyrosine activation motifs ITAM in the cytoplasmic domain of the TCR, ZAP-70, which is recruited to phosphorylated ITAM, and phosphorylates...
Molecular Organization and Assembly of the Presynaptic Active Zone of
Anna Fejtova K Eckart D. Gundelfinger Department of Neurochemistry and Molecular Biology, Brennecke Str. 6, Abstract At chemical synapses, neurotransmitter is released at a restricted region of the presynaptic plasma membrane, called the active zone. At the active zone, a matrix of proteins is assembled, which is termed the presynaptic grid or cytomatrix at the active zone CAZ . Components of the CAZ are thought to localize and organize the synaptic vesicle cycle, a series of membrane...
Gap Junctions in Glial Cells
Although the term electrical synapse refers primarily to neuronal cell interaction, gap junctions being the structural equivalent of electrical synapses are not only observed on neuronal cells but also on most other cell types in the CNS Fig. 2 . We will therefore provide a short summary of glial connex-ins in the adult central nervous system. The connexin proteins expressed by macroglia cells include Cx26, Cx30, and Cx43 in astrocytes, and Cx29, Cx32, and Cx47 in oligodendrocytes Fig. 2 . In...
T Cell Activation in the Lymph Node A Marketplace Analogy
In order to get activated, T cells needs to find APC with the correct peptide-MHC complexes on their surface. However, there exists an intrinsic information problem. A T cell does not have any knowledge of whether the antigen for which its TCR is specific has been taken up somewhere in the body. Nor does a DC know which T cell is specific for the pathogen that it just had phagocy-tosed, and whose processed peptide antigens are now presented on its MHC molecules. Likewise, a B cell cannot tell...
Postsynaptic Signaling and PSD Proteins
The strength and plasticity of excitatory synapses are regulated by signaling pathways in dendritic spines Kennedy et al. 2005 . The molecular organization of these pathways is coordinated by PSD proteins. A well-known example is the association of PSD-95 with neuronal nitric oxide synthase, which couples NMDAR activation to nitric oxide generation Aarts et al. 2002 Bredt 2005 . SynGAP is a neuron-specific GAP for Ras and Rap small GTPases Chen et al. 1998 Kim et al. 1998 , which regulate AMPAR...
References 1
Angelotti TP, Macdonald RL 1993 Assembly of GABAA receptor subunits alpha 1 beta 1 and alpha 1 beta 1 gamma 2S subunits produce unique ion channels with dissimilar single-channel properties. J Neurosci 13 1429-1440 Beck M, Brickley K, Wilkinson HL, Sharma S, Smith M, Chazot PL, Pollard S, Stephenson FA 2002 Identification, molecular cloning, and characterization of a novel GABAA receptor-associated protein, GRIF-1. J Biol Chem 277 30079-30090 Bedford FK, Kittler JT, Muller E, Thomas P, Uren JM,...
TenascinR GABAergic Transmission and Metaplasticity
Another example of how ECM molecules affect GABAergic transmission is provided by the glycoprotein tenascin-R TN-R . TN-R is enriched at the nodes of Ranvier and in the perineuronal nets and is essential for assembly of these nets since distribution of net-associated ECM molecules is altered in TN-R-deficient mice Weber et al. 1999 Bruckner et al. 2000 . Furthermore, a recent study revealed rather general changes in the organization of extracellular space in TN-R KO brains, as detected via...
Lecticans Differentially Contribute to Synapse Formation and Function
A final group of extracellular molecules to be discussed in the context of synaptic functioning are the CSPGs of the lectican family for a review see Yamaguchi 2000 . This family comprises four abundant components of brain ECM aggrecan and versican as broadly expressed CSPGs and neurocan and brevican as nervous system-specific family members. Because of manifold post-translational modifications each lectican occurs in several isoforms alternative splicing, differential addition of CS side...
Costimulation by Endothelial Cells
Co-stimulation by antigen-presenting cells is required to stimulate naive or resting T lymphocytes and may be further categorized in membrane-bound co-stimulatory molecules such as CD80, CD86 and CD40 or soluble co-stimulation most importantly interleukin-12 IL-12 . Endothelial cells from humans Karmann et al. 1995 and mice Grewal and Flavell 1998 express CD40 and may thus serve to interact with CD154 CD40L -expressing T lymphocytes. The induction of CD154 expression on T lymphocytes is driven...
Challenges in Expression Analysis of Gap Junction Proteins
Quantitative and qualitative changes of connexin expression were demonstrated under certain developmental and pathological circumstances see above . Thus, analysis of gap junctional coupling can only provide a depiction of the actual connexin expression, irrespective of a putative diverse molecular make-up at different developmental stages or under the influence of pathological conditions including de- and regeneration. Examples of pathological changes in connexin expression include an increase...
and Immune System
With 28 Figures, 8 in Color, and 3 Tables Professor Dr. Eckart D. GuNDeLFiNgeR Dr. Constanze I. Seidenbecher Abteilung Neurochemie und Molekularbiologie Institut f r Immunologie Otto-von-Guericke-Universit t Magdeburg Leipzigerstrasse 44 3120 Magdeburg ISBN-10 3-540-36828-0 Springer Berlin Heidelberg New York ISBN-13 978-3-540-36828-1 Springer Berlin Heidelberg New York Library of Congress Control Number 2006932575 This work is subject to copyright. All rights are reserved, whether the whole or...
HBGAM and Nsyndecan in Synaptic Plasticity
Another molecule that binds to heparin is the heparin-binding growth-associated molecule HB-GAM . It has been implicated in the regulation of neurite outgrowth, axon guidance and synaptogenesis in vitro for a review see Rauvala and Peng 1997 . HB-GAM is expressed in an activity-dependent manner Lauri et al. 1996 . In the adult hippocampus, application of HB-GAM inhibited NMDA receptor-dependent LTP, but did not affect L-type VDCC-dependent LTP, that was induced by application of the K channel...
Synaptic Functions of Reelin
Integrins have also been recognized as receptors for an ECM glycoprotein called reelin, named after the spontaneously occurring reeler mouse mutant, which shows abnormal migration of neurons during embryonic development. These deficits result in an outside-in instead of inside-out positioning of migrating neuronal cell bodies in the cerebral cortex. Strikingly, mice deficient in receptors for reelin, the very low density lipoprotein VLDL receptor and apoE receptor 2 apoER2 , and cytoplasmic...
Extracellular Matrix and Synaptic Functions
Alexander Dityatev1 K Renato Frischknecht2 Constanze I. Seidenbecher2 1 Institut f r Neurophysiologie und Pathophysiologie, Universit tsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany a.dityatev uke.uni-hamburg.de 2Leibniz-Institut f r Neurobiologie, Brenneckestr. 6, 39118 Magdeburg, Germany Abstract Comprehensive analysis of neuromuscular junction formation and recent data on synaptogenesis and long-term potentiation in the central nervous system revealed a number of...
Some History on Electrical Synapses
In general, synapses can be defined as specialized sites of functional interaction between neurons. As neuronal gap junctions comprise defined areas of neuronal membranes, provide for direct cell-to-cell contact, and enable the exchange of molecules between neurons, they fulfil the requirements for being designated synaptic contacts. Initially, their predominant function was thought to be the intercellular transport of ions, and neuronal gap junctions were therefore named electrical synapses....
Spine Formation and PSD Proteins
Polymerization of F-actin in dendritic spines regulates spine morphogenesis and synaptic plasticity Segal 2005 . The Rac1, RhoA, and Cdc42 Rho family small GTPases are important regulators of F-actin remodeling in spines. For instance, Rac1 promotes spine density and maturation, whereas RhoA has an opposite role Luo et al. 1996 Nakayama et al. 2000 Tashiro et al. 2000 Tashiro and Yuste 2004 . PSD proteins directly associate with the Racl signaling pathway proteins Fig. 2 , promoting their...
Contents
of the Postsynaptic Density of Excitatory Brain Synapses Eunjoon Kim, Jaewon 1 Introduction 2 Components of the PSD 3 Assembly of the 4 Synaptic Adhesion and PSD Proteins 4 5 Membrane Proteins and PSD Proteins 5 6 Spine Formation and PSD 7 Postsynaptic Signaling and PSD Proteins 7 8 Regulation of Synaptic Transmission and Plasticity by PSD 9 Dynamic Regulation of the Assembly of the PSD 11 10 Transport of PSD Proteins by Motor Proteins 12 Molecular Organization and Assembly of the Central...