Anterograde C1ql1 Signaling Is Required in Order to Determine and Maintain a Single-Winner Climbing Fiber in the Mouse Cerebellum

Kakegawa, Wataru; Mitakidis, Nikolaos; Miura, Eriko; Abe, Manabu; Matsuda, Keiko; Takeo, Yukari H.; Kohda, Kazuhisa; Motohashi, Junko; Takahashi, Akiyo; Nagao, Soichi; Muramatsu, Shin‐ichi; Watanabe, Masahiko; Sakimura, Kenji; Aricescu, A. Radu; Yuzaki, Michisuke

doi:10.1016/j.neuron.2014.12.020

Cited by 159 publications

(171 citation statements)

References 43 publications

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“…We found that the GluK5extra-Fc pull-downed HA-C1QL3/nCLP3 compared to control protein (bovine serum albumin) in a calcium dependent manner (Figure 7E). Similar calcium–dependent oligomerization and interaction of C1QL family proteins with other potential receptors has previously been reported (Bolliger et al, 2011; Kakegawa et al, 2015; Ressl et al, 2015). We next confirmed that C1QL2/nCLP2 signal is enriched in the stratum lucidum of wild-type mice using anti C1QL2 antibody (Figure 7F).…”

Section: Resultssupporting

confidence: 85%

Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

et al. 2016

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Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors have restricted synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilized kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

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Section: Resultssupporting

confidence: 85%

Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

et al. 2016

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“…Subsequent pioneering in vivo experiments revealed that postsynaptic BAI3 physiologically functions as a C1ql1 receptor in climbing-fiber synapses in cerebellum, and that deletion of either BAI3 or C1ql1 causes a loss of climbing-fiber synapses (Kakegawa et al, 2015; Sigoillot et al, 2015), proving a role for C1ql’s in synapse formation. Similarly, C1ql3 deletion from amygdala neurons was shown to suppress the number of synapses formed by C1ql3-expressing amygdala neuron on prefrontal cortex neurons, confirming a synaptic role for C1ql’s (Martinelli et al, 2016).…”

Section: Calsynteninsmentioning

confidence: 99%

Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

Südhof

2017

Cell

608

691

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Synapses are specialized junctions between neurons in brain that transmit and compute information, thereby connecting neurons into millions of overlapping and interdigitated neural circuits. Here we posit that the establishment, properties, and dynamics of synapses are governed by a molecular logic that is controlled by diverse trans-synaptic signaling molecules. Neurexins, expressed in thousands of alternatively spliced isoforms, are central components of this dynamic code. Presynaptic neurexins regulate synapse properties via differential binding to multifarious postsynaptic ligands, such as neuroligins, cerebellin/GluD complexes, and latrophilins, thereby shaping the input/output relations of their resident neural circuits. Mutations in genes encoding neurexins and their ligands are associated with diverse neuropsychiatric disorders, especially schizophrenia, autism, and Tourette syndrome. Thus, neurexins nucleate an overall trans-synaptic signaling network that controls synapse properties, that thereby determines the precise responses of synapses to spike patterns in a neuron and circuit, and that is vulnerable to impairments in neuropsychiatric disorders.

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“…The function of these genes within the context of supragranular laminar circuitry has not been well characterized in model systems, because by definition they are not prominently expressed in upper layers in mouse. However, the C1QL family is thought to play a critical role in synapse formation and maintenance of synapses between climbing fibers from the inferior olive and Purkinje cells in the cerebellum (63), as well as in postnatal synapse elimination between retinal ganglion cells and the lateral geniculate nucleus (64). It is also expressed in dentate gyrus granule cells (65).…”

Section: And 7)mentioning

confidence: 99%

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Krienen

Yeo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

201

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The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.corticocortical connectivity | human transcriptome | association cortex | supragranular | brain evolution P atterns of gene expression in the cerebral cortex are generally conserved across species, reflecting strong constraints in the development and evolution of cortical architecture (1-6). Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7, 8). Molecular variation often takes the form of graded expression along a principal axis, in many cases appearing as rostrocaudal gradients across the cortex (8). The strong tendency for transcriptional variation to follow spatial proximity in the adult cortex likely reflects both functional gradients, as well as their developmental origins in terms of physical and temporal adjacency during neurogenesis of cells destined for neighboring locations in the cortex (at least for cells derived from the ventricular proliferative pool) (7).Spatial proximity likely captures the major features governing how molecular profiles vary across the cortex in all species, including humans. However, the expansion of the cerebral cortex in primates...

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Anterograde C1ql1 Signaling Is Required in Order to Determine and Maintain a Single-Winner Climbing Fiber in the Mouse Cerebellum

Cited by 159 publications

References 43 publications

Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

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