Bassoon, a Novel Zinc-finger CAG/Glutamine-repeat Protein Selectively Localized at the Active Zone of Presynaptic Nerve Terminals

Dieck, Susannetom; Sanmarti-Vila, Lydia; Langnaese, Kristina; Richter, Karin; Kindler, Stefan; Soyke, Antje; Wex, Heike; Smalla, Karl‐Heinz; Kämpf, Udo; Fränzer, Jürgen-Theodor; Stümm, Markus; Garner, Craig C.; Gundelfinger, Eckart D.

doi:10.1083/jcb.142.2.499

Cited by 429 publications

(424 citation statements)

References 51 publications

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“…To examine the effect of Arg-61 apoE on the active zone, immunostaining was performed for Bassoon, an active zone component involved in structural organization and neurotransmitter release [24]. Bassoon-immunoreactive presynaptic boutons were less numerous in the hippocampus of Arg-61 apoE mice than WT mice (CA3, 26.3 ± 0.9% vs. 28.7 ± 0.7%, P < 0.05; CA1, 27.1 ± 0.8% vs. 29.7 ± 0.8%, P = .05); no significant difference was observed in the neocortex (27.6 ± 1.5% vs. WT 29.5 ± 2.2%) ( Figure 4A, B).…”

Section: Presynaptic Synaptophysin Levels In Arg-61 Mice Decline Withmentioning

confidence: 99%

Apolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice

Zhong

Scearce‐Levie

Ramaswamy

et al. 2008

Alzheimer's & Dementia

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BackgroundApolipoprotein E4 (apoE4), the major genetic risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases, has three structural and biophysical properties that distinguish it from the other isoforms—domain interaction, reduced stability, and lack of cysteine. Assessing their relative contributions to effects of apoE4‐associated pathogenesis in AD is important from a mechanistic and therapeutic perspective, that is not possible using human apoE transgene or knock‐in models.MethodsWe analyzed Arg‐61 apoE mice, a gene‐targeted model that selectively displays domain interaction.ResultsThe mice displayed age‐dependent loss of the synaptic protein synaptophysin in neocortex and hippocampus and had lower levels of the postsynaptic neuroligin‐1. Activation of dentate gyrus granule neurons increased Arc expression 3.5‐fold in wildtype mice but only 2.3‐fold in Arg‐61 mice. The losses of synaptic proteins caused a mild memory deficit in Arg‐61 mice in the water‐maze test. Since synaptic integrity requires efficient glutamate uptake, we measured astrocyte glutamate transporter 1 in the hippocampus. The level was reduced in Arg‐61 mice, suggesting that inefficient glutamate uptake by astrocytes causes chronic excitotoxicity. Consistent with the reduced secretion of Arg‐61 apoE by astrocytes in this model, cholesterol secretion was also reduced 34%. This reduction could also contribute to the synaptic deficits by limiting the availability of cholesterol for neuronal repair.ConclusionsDomain interaction in the absence of other structural characteristics of apoE4 is sufficient to cause synaptic pathology and functional synaptic deficits, potentially associated with astrocyte dysfunction and impaired maintenance of neurons. Therapeutic targeting of domain interaction might blunt effects of apoE4 in neurodegenerative disease.

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Section: Presynaptic Synaptophysin Levels In Arg-61 Mice Decline Withmentioning

confidence: 99%

Apolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice

Zhong

Scearce‐Levie

Ramaswamy

et al. 2008

Alzheimer's & Dementia

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“…Subcellular membrane protein fractions were obtained essentially as described previously (tom Dieck et al 1998) and digested with chondroitinase ABC at 0.1 U per 60 lg protein in 40 mM Tris-HCl, 40 mM sodium acetate, pH 8.0, for 90 min at 37°C. In the partitioning experiment 600 lg rat brain homogenate was adjusted to 40 mM Tris-HCl, 40 mM sodium acetate, pH 8.0, centrifuged at 14 000 g for 20 min, and both the soluble and the resuspended particulate fractions were incubated with chondroitinase ABC.…”

Section: Radiochemicalsmentioning

confidence: 99%

Brevican isoforms associate with neural membranes

Seidenbecher

Smalla

Fischer

et al. 2002

Journal of Neurochemistry

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Brevican is a neural-specific proteoglycan of the brain extracellular matrix, which is particularly abundant in the terminally differentiated CNS. It is expressed by neuronal and glial cells, and as a component of the perineuronal nets it decorates the surface of large neuronal somata and primary dendrites. One brevican isoform harbors a glycosylphosphatidylinositol anchor attachment site and, as shown by ethanolamine incorporation studies, is indeed glypiated in stably transfected HEK293 cells as well as in oligodendrocyte precursor Oli-neu cells. The major isoform is secreted into the extracellular space, although a significant amount appears to be tightly attached to the cell membrane, as it floats up in sucrose gradients. Flotation is sensitive to detergent treatment.Brevican is most prominent in the microsomal, light membrane and synaptosomal fractions of rat brain membrane preparations. The association with the particulate fraction is in part sensitive to chondroitinase ABC and phosphatidylinositolspecific phospholipase C treatment. Furthermore, brevican staining on the surface of hippocampal neurons in culture is diminished after hyaluronidase or chondroitinase ABC treatment. Taken together, this could provide a mechanism by which perineuronal nets are anchored on neuronal surfaces.

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“…Several Bassoon antibodies were used: a rabbit Bassoon antisera (1:100) that was described previously (tom Dieck et al, 1998) and mouse monoclonal anti-Bassoon (1:500 to1:2000; StressGen, Victoria, British Columbia, Canada). After three washes in PBS, neurons were incubated at least 30 min in blocking solution and then incubated with secondary antibodies in blocking solution for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%