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Postsynaptic Differentiation (postsynaptic + differentiation)
Selected AbstractsEffects of agrin on the expression and distribution of the water channel protein aquaporin-4 and volume regulation in cultured astrocytesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2007Susan Noell Abstract Agrin is a heparan sulfate proteoglycan of the extracellular matrix and is known for organizing the postsynaptic differentiation of the neuromuscular junction. Increasing evidence also suggests roles for agrin in the developing CNS, including the formation and maintenance of the blood,brain barrier. Here we describe effects of agrin on the expression and distribution of the water channel protein aquaporin-4 (AQP4) and on the swelling capacity of cultured astrocytes of newborn mice. If astrocytes were cultured on a substrate containing poly dl -ornithine, anti-AQP4 immunoreactivity was evenly and diffusely distributed. If, however, astrocytes were cultured in the presence of agrin-conditioned medium, we observed an increase in the intensity of AQP4-specific membrane-associated staining. Freeze-fracture studies revealed a clustering of orthogonal arrays of particles, representing a structural equivalent of AQP4, when exogenous agrin was present in the astrocyte cultures. Neuronal and non-neuronal agrin isoforms (agrin A0B0 and agrin A4B8, respectively) were able to induce membrane-associated AQP4 staining. Water transport capacity as well as the density of orthogonal arrays of intramembranous particles was increased in astrocytes cultured with the neuronal agrin isoform A4B8, but not with the endothelial and meningeal isoform A0B0. RT-PCR demonstrated that agrin A4B8 increased the level of the M23 splice variant of AQP4 and decreased the level of the M1 splice variant of AQP4. Implications for the regulation and maintenance of the blood,brain barrier including oedema formation under pathological conditions are discussed. [source] Molecular regulation of postsynaptic differentiation at the neuromuscular junctionIUBMB LIFE, Issue 11 2005Raghavan Madhavan Abstract The neuromuscular junction (NMJ) is a synapse that develops between a motor neuron and a muscle fiber. A defining feature of NMJ development in vertebrates is the re-distribution of muscle acetylcholine (ACh) receptors (AChRs) following innervation, which generates high-density AChR clusters at the postsynaptic membrane and disperses aneural AChR clusters formed in muscle before innervation. This process in vivo requires MuSK, a muscle-specific receptor tyrosine kinase that triggers AChR re-distribution when activated; rapsyn, a muscle protein that binds and clusters AChRs; agrin, a nerve-secreted heparan-sulfate proteoglycan that activates MuSK; and ACh, a neurotransmitter that stimulates muscle and also disperses aneural AChR clusters. Moreover, in cultured muscle cells, several additional muscle- and nerve-derived molecules induce, mediate or participate in AChR clustering and dispersal. In this review we discuss how regulation of AChR re-distribution by multiple factors ensures aggregation of AChRs exclusively at NMJs. IUBMB Life, 57: 719-730, 2005 [source] Seeking long-term relationship: axon and target communicate to organize synaptic differentiationJOURNAL OF NEUROCHEMISTRY, Issue 5 2006Michael A. Fox Abstract Synapses form after growing axons recognize their appropriate targets. The subsequent assembly of aligned pre and postsynaptic specializations is critical for synaptic function. This highly precise apposition of presynaptic elements (i.e. active zones) to postsynaptic specializations (i.e. neurotransmitter receptor clusters) strongly suggests that communication between the axon and target is required for synaptic differentiation. What trans-synaptic factors drive such differentiation at vertebrate synapses? First insights into the answers to this question came from studies at the neuromuscular junction (NMJ), where axon-derived agrin and muscle-derived laminin ,2 induce post and presynaptic differentiation, respectively. Recent work has suggested that axon- and target-derived factors similarly drive synaptic differentiation at central synapses. Specifically, WNT-7a, neuroligin, synaptic cell adhesion molecule (SynCAM) and fibroblast growth factor-22 (FGF-22) have all been identified as target-derived presynaptic organizers, whereas axon-derived neuronal activity regulated pentraxin (Narp), ephrinB and neurexin reciprocally co-ordinate postsynaptic differentiation. In addition to these axon- and target-derived inducers of synaptic differentiation, factors released from glial cells have also been implicated in regulating synapse assembly. Together, these recent findings have profoundly advanced our understanding of how precise appositions are established during vertebrate nervous system development. [source] An interdomain disulfide bridge links the NtA and first FS domain in agrinPROTEIN SCIENCE, Issue 12 2009Ainsley A. McFarlane Abstract Agrin is a multidomain heparan sulfate proteoglycan involved in postsynaptic differentiation at the neuromuscular junction. Binding of agrin to synaptic basal lamina is mediated by the N -terminal agrin (NtA) domain. The NtA domain of agrin is followed by a tandem of nine follistatin-like (FS) domains forming a rod-like spacer to the laminin G-like domains of the molecule. Here we report that the most C -terminal cysteine residue of NtA (Cys123) forms an interdomain disulfide bond with the FOLN subdomain of the FS module. Remarkably, this single cysteine is flanked by Leu117 and Val124, which are two essential ,-branched amino acids forming the heterocomplex of NtA with the ,1 chain of laminin. Moreover, we show that this covalent linkage compensates for the seven amino acid residue splice insert at the very C-terminal helix H3 and causes a rigid interface between NtA and FS independent of the alternative mRNA splice event. These results suggest that the interdomain disulfide bond between the NtA and the first FS domain might be important for the proper folding of agrin. [source] | ||||||||||