scholarly journals Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters

2019 ◽  
Vol 218 (8) ◽  
pp. 2677-2698 ◽  
Author(s):  
Justin H. Trotter ◽  
Junjie Hao ◽  
Stephan Maxeiner ◽  
Theodoros Tsetsenis ◽  
Zhihui Liu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Active Zone ◽  
Cell Adhesion Molecules ◽  
Super Resolution ◽  
Adult Brain ◽  
Excitatory Synapses ◽  
Synaptic Localization ◽  
Organizational Feature ◽  
Super Resolution Microscopy

Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate that neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature of synaptic architecture. Synapses generally contain a single nanocluster that comprises more than four neurexin-1 molecules and that also includes neurexin-2 and/or neurexin-3 isoforms. Moreover, we find that neurexin-1 is physiologically cleaved by ADAM10 similar to its ligand neuroligin-1, with ∼4–6% of neurexin-1 and ∼2–3% of neuroligin-1 present in the adult brain as soluble ectodomain proteins. Blocking ADAM10-mediated neurexin-1 cleavage dramatically increased the synaptic neurexin-1 content, thereby elevating the percentage of Homer1(+) excitatory synapses containing neurexin-1 nanoclusters from 40–50% to ∼80%, and doubling the number of neurexin-1 molecules per nanocluster. Taken together, our results reveal an unexpected nanodomain organization of synapses in which neurexin-1 is assembled into discrete presynaptic nanoclusters that are dynamically regulated via ectodomain cleavage.

scholarly journals Proteomic and functional analyses of the periodic membrane skeleton in neurons

2020 ◽  
Author(s):  
Ruobo Zhou ◽  
Boran Han ◽  
Roberta Nowak ◽  
Yunzhe Lu ◽  
Evan Heller ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Super Resolution ◽  
Membrane Skeleton ◽  
Interacting Proteins ◽  
Functional Roles ◽  
Genetic Perturbations ◽  
Resolution Imaging ◽  
Functional Analyses

AbstractActin, spectrin, and associated molecules form a membrane-associated periodic skeleton (MPS) in neurons. The molecular composition and functions of the MPS remain incompletely understood. Here, using co-immunoprecipitation and mass spectrometry, we identified hundreds of candidate MPS-interacting proteins that span diverse functional categories. We validated representative proteins in several of these categories, including previously unknown MPS structural components, as well as motor proteins, cell adhesion molecules, ion channels, and signaling proteins, demonstrating periodic distributions of ∼20 proteins in neurons using super-resolution imaging. Genetic perturbations of the MPS and its interacting proteins further suggested functional roles of the MPS in axon-axon and axon-dendrite interactions and in axon diameter regulation, and implicated the involvement of MPS interactions with cell adhesion molecules and non-muscle myosin in these roles. These results provide new insights into the interactome of the MPS, and suggest new functions of the MPS in neurons.

scholarly journals Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules.

1993 ◽  
Vol 120 (3) ◽  
pp. 815-824 ◽  
Author(s):  
M Grumet ◽  
A Flaccus ◽  
R U Margolis
Keyword(s):  
Cell Adhesion ◽  
Chondroitin Sulfate ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Core Protein ◽  
Functional Characterization ◽  
Adult Brain ◽  
Chondroitin Sulfate Proteoglycans ◽  
Core Proteins ◽  
Cell Adhesion And Migration

Ng-CAM and N-CAM are cell adhesion molecules (CAMs), and each CAM can bind homophilically as demonstrated by the ability of CAM-coated beads (Covaspheres) to self-aggregate. We have found that the extent of aggregation of Covaspheres coated with either Ng-CAM or N-CAM was strongly inhibited by the intact 1D1 and 3F8 chondroitin sulfate proteoglycans of rat brain, and by the core glycoproteins resulting from chondroitinase treatment of the proteoglycans. Much higher concentrations of rat chondrosarcoma chondroitin sulfate proteoglycan (aggrecan) core proteins had no significant effect in these assays. The 1D1 and 3F8 proteoglycans also inhibited binding of neurons to Ng-CAM when mixtures of these proteins were adsorbed to polystyrene dishes. Direct binding of neurons to the proteoglycan core glycoproteins from brain but not from chondrosarcoma was demonstrated using an assay in which cell-substrate contact was initiated by centrifugation, and neuronal binding to the 1D1 proteoglycans was specifically inhibited by the 1D1 monoclonal antibody. Different forms of the 1D1 proteoglycan have been identified in developing and adult brain. The early postnatal form (neurocan) was found to bind neurons more effectively than the adult proteoglycan, which represents the C-terminal half of the larger neurocan core protein. Our results therefore indicate that certain brain proteoglycans can bind to neurons, and that Ng-CAM and N-CAM may be heterophilic ligands for neurocan and the 3F8 proteoglycan. The ability of these brain proteoglycans to inhibit adhesion of cells to CAMs may be one mechanism to modulate cell adhesion and migration in the nervous system.

scholarly journals Expression sequences and distribution of two primary cell adhesion molecules during embryonic development of Xenopus laevis.

1987 ◽  
Vol 105 (5) ◽  
pp. 2359-2372 ◽  
Author(s):  
G Levi ◽  
K L Crossin ◽  
G M Edelman
Keyword(s):  
Cell Adhesion ◽  
Xenopus Laevis ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
Adult Brain ◽  
Neural Ectoderm ◽  
Sensory Layer ◽  
Endodermal Cells

Studies of chicken embryos have demonstrated that cell adhesion molecules are important in embryonic induction and are expressed in defined sequences during embryogenesis and histogenesis. To extend these observations and to provide comparable evidence for heterochronic changes in such sequences during evolution, the local distributions of the neural cell adhesion molecule (N-CAM) and of the liver cell adhesion molecule (L-CAM) were examined in Xenopus laevis embryos by immunohistochemical and biochemical techniques. Because of the technical difficulties presented by the existence of multiple polypeptide forms of CAMs and by autofluorescence of yolk-containing cells, special care was taken in choosing and characterizing antibodies, fluorophores, and embedding procedures. Both N-CAM and L-CAM were found at low levels in pregastrulation embryos. During gastrulation, N-CAM levels increased in the presumptive neural epithelium and decreased in the endoderm, but L-CAM continued to be expressed in all cells including endodermal cells. During neurulation, the level of N-CAM expression in the neural ectoderm increased considerably, while remaining constant in non-neural ectoderm and diminishing in the somites; in the notochord, N-CAM was expressed transiently. Prevalence modulation was also seen at all sites of secondary induction: both CAMs increased in the sensory layer of the ectoderm during condensation of the placodes. During organogenesis, the expression of L-CAM gradually diminished in the nervous system while N-CAM expression remained high. In all other organs examined, the amount of one or the other CAM decreased, so that by stage 50 these two molecules were expressed in non-overlapping territories. Embryonic and adult tissues were compared to search for concordance of CAM expression at later stages. With few exceptions, the tissue distributions of N-CAM and L-CAM were similar in the frog and in the chicken from early times of development. In contrast to previous observations in the chicken and in the mouse, N-CAM expression was found to be high in the adult liver of Xenopus, whereas L-CAM expression was low. In the adult brain, N-CAM was expressed as three components of apparent molecular mass 180, 140, and 120 kD, respectively; in earlier stages of development only the 140-kD component could be detected. In the liver, a single N-CAM band appears at 160 kD, raising the possibility that this band represents an unusual N-CAM polypeptide. L-CAM appeared at all stages as a 124-kD molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals PSD-95 binding dynamically regulates NLGN1 trafficking and function

2019 ◽  
pp. 201821775 ◽  
Author(s):  
Jaehoon Jeong ◽  
Saurabh Pandey ◽  
Yan Li ◽  
John D. Badger ◽  
Wei Lu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
Surface Expression ◽  
Scaffolding Protein ◽  
Excitatory Synapses ◽  
Signaling Proteins ◽  
Synaptic Development ◽  
Synaptic Localization ◽  
And Function

PSD-95 is a scaffolding protein that regulates the synaptic localization of many receptors, channels, and signaling proteins. The NLGN gene family encodes single-pass transmembrane postsynaptic cell adhesion molecules that are important for synapse assembly and function. At excitatory synapses, NLGN1 mediates transsynaptic binding with neurexin, a presynaptic cell adhesion molecule, and also binds to PSD-95, although the relevance of the PSD-95 interaction is not clear. We now show that disruption of the NLGN1 and PSD-95 interaction decreases surface expression of NLGN1 in cultured neurons. Furthermore, PKA phosphorylates NLGN1 on S839, near the PDZ ligand, and dynamically regulates PSD-95 binding. A phosphomimetic mutation of NLGN1 S839 significantly reduced PSD-95 binding. Impaired NLGN1/PSD-95 binding diminished synaptic NLGN1 expression and NLGN1-mediated synaptic enhancement. Our results establish a phosphorylation-dependent molecular mechanism that regulates NLGN1 and PSD-95 binding and provides insights into excitatory synaptic development and function.

Cell Adhesion Molecules: Selectins and Integrins

1999 ◽  
Vol 19 (5-6) ◽  
pp. 41 ◽  
Author(s):  
Francisco Sanchez-Madrid ◽  
Roberto González-Amaro
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules

ROCK2 Regulates the Expression of Cell Adhesion Molecules and Cell-to-Cell Adhesion in Vascular Endothelial Cells

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 476-P
Author(s):  
YUSUKE TAKEDA ◽  
KEIICHIRO MATOBA ◽  
DAIJI KAWANAMI ◽  
YOSUKE NAGAI ◽  
TOMOYO AKAMINE ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Cell To Cell Adhesion
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