Protein kinase C phosphorylation of a γ-protocadherin c-terminal lipid binding domain regulates focal adhesion kinase inhibition and dendrite arborization. Protocadherin clusters and cell adhesion kinase regulate dendrite complexity through Rho GTPase. Phosphorylation of protocadherin proteins by the receptor tyrosine kinase Ret. The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins. Routine single particle cryoEM sample and grid characterization by tomography. Protocadherin cis-dimer architecture and recognition unit diversity. Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4. γ-Protocadherin structural diversity and functional implications. Structural basis of diverse homophilic recognition by clustered α- and β-protocadherins. Structure and sequence analyses of clustered protocadherins reveal antiparallel interactions that mediate homophilic specificity. Molecular logic of neuronal self-recognition through protocadherin domain interactions. Combinatorial homophilic interaction between γ-protocadherin multimers greatly expands the molecular diversity of cell adhesion. Combinatorial effects of alpha- and gamma-protocadherins on neuronal survival and dendritic self-avoidance. Developmental epigenetic modification regulates stochastic expression of clustered protocadherin genes, generating single neuron diversity. Structural origins of clustered protocadherin-mediated neuronal barcoding. Single-cell identity generated by combinatorial homophilic interactions between α, β, and γ protocadherins. Molecular codes for neuronal individuality and cell assembly in the brain. Chemoaffinity revisited: dscams, protocadherins, and neural circuit assembly. Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. A striking organization of a large family of human neural cadherin-like cell adhesion genes. Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly. Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function. Homophilic protocadherin cell–cell interactions promote dendrite complexity. Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Our results suggest that the formation of ordered linear assemblies by clustered protocadherins represents the initial self-recognition step in neuronal avoidance, and thus provide support for the isoform-mismatch chain-termination model of protocadherin-mediated self-recognition, which depends on these linear chains 11.
These linear assemblies pack against each other as parallel arrays to form larger two-dimensional structures between membranes. Using cryo-electron tomography, we show that clustered protocadherin γB6 ectodomains tethered to liposomes spontaneously assemble into linear arrays at membrane contact sites, in a configuration that is consistent with the assembly observed in the crystal structure. We determine the crystal structure of the clustered protocadherin γB4 ectodomain, which reveals a zipper-like lattice that is formed by alternating cis and trans interactions.
Here we determine the molecular arrangement of full-length clustered protocadherin ectodomains in single-isoform self-recognition complexes, using X-ray crystallography and cryo-electron tomography.
Although these interactions have previously been characterized in isolation 15, 17, 18, 19, 20, structures of full-length protocadherin ectodomains have not been determined, and how these two interfaces engage in self-recognition between neuronal surfaces remains unknown. Protocadherins form isoform-promiscuous cis dimers and isoform-specific homophilic trans dimers 10, 14, 15, 16, 17, 18, 19, 20. Avoidance is observed between neurons that express identical protocadherin repertoires 2, 5, and single-isoform differences are sufficient to prevent self-recognition 10. Avoidance among self neurites is mediated by stochastic cell-surface expression of combinations of about 60 isoforms of α-, β- and γ-clustered protocadherin that provide mammalian neurons with single-cell identities 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13.
#Transformice codes for points 2019 free
These processes facilitate dendritic arborization 2, 3, prevent formation of autapses 4 and allow free interaction among non-self neurons 1, 2, 4, 5. Neurite self-recognition and avoidance are fundamental properties of all nervous systems 1.
0 kommentar(er)
