Structural Biochemistry/Ligand-Binding Site and Glutamate Receptor Trafficking
The Ligand-Binding Site and Glutamate Receptor Trafficking:
The glutamate receptors' extracellular domains share homology with bacterial periplasmic binding proteins. Due to this observation, many studies have started for the ligand-binding domains of AMPA receptor subunits. To further expand on these observations, Stephanie J. Mah and others have used the kainate receptor subunit, glutamate receptor 6 (GluR6) through the mutating preserved residues (R523, T690, or E738) in the ligand-binding pocket. After this, functional responses and agonist binding were removed, however more importantly homomeric mutant receptors were kept in the endoplasmic reticulum. These mutants created oligomers in the ER and were brought about to the surface when expressed with wild-type GLuR6 subunits. Due to this, the retention did not make any apparent contributions to the misfolding. It is assumed and suggested that the ER can supervise the functional state of fully assembled GluR channels and keep those that are unable to bind agonist, most likely due to high intracellular glutamate causes nascent receptor to be exported in their bound conformation.
A Growth Cone Turn Signal:
Axons are able to extend and retract as they search for their targets. The signaling mechanisms that assist axon growth includes Rho GT-Pases and cytoplasmic calcium transients. In reaction to extracellular factors, the Rho GTPases work as switches that will activate the cytoskeletal rearrangement required for an axonal direction change. It was suggested that a mechanism that links Rho GTPases and calcium in the turning of growth cones. A cultured Xenopus spinal neurons with an extracellular ryanodine gradient was presented, allowing the activation of the release of calcium in an asymmetrical-like pattern across the growth cone; the growth cone then turns toward the source. This turning of the growth cone is reliant on calcium-dependent upregulation of the Rho GTPase, Cdc42, which is most likely via protein kinase C- and Ca2+/calmodulin-dependent protein kinase II-dependent phosphorylation. It was concluded that calcium is what triggers the turn signal.
Horizontal Cells Define Their Turf:
On the retina, horizontal cell dendrites disperse evenly across the retina. Benjamin E. Reese and others utilized several strains of mice in which, although a large discrepancy in horizontal cell number, dendrites were kept equally spread. For that reason, the size of the dendritic fields varied inversely with cell number. Cone photoreceptors were ablated using cone-specific diphtheria toxin expression; this was done so that the influence could be tested. With the absence of cone synapses, the organization of horizontal cells in the outer plexiform layer was normal. Furthermore the trade mark size of the dendritic field was normal as well. The dendrites in the retinas without cones divided greatly and showed no clusters of terminals that are normally observed at cone pedicles.
Neurobiology of DiseaseEdit
Neonatal Coxsackievirus Infection of Neuronal Progenitors:
Coxsackievirus B (CVB) infections have the ability to cause severe consequences such as meningoencephalitis, especially in new-born babies and young children. Ralph Feuer and others were able to track the dangerous path of CVB3 infections in neonatal mice. From their observations, the virus seemed to have preferred to attack dividing neuronal progenitor cells in the subventricular zone (SVZ). Infected cells were no longer being produced in the SVZ, based on their lack of immunoreactivity to Ki67, a nuclear antigen. On the other, they were still able to keep their migratory capacity. The infected cells trailed along the rostral migratory stream or radial glial cells to arrive at the olfactory bulb or cerebral cortex, respectively. The infected cells seem to also differentiate normally, however they were still capable of creating viral proteins. Through this process, the virus then latches onto proliferating neuronal precursors only to cause virus-induced lysis of mature cells at the end. It is suggested that depletion of infected mature cells are a possible cause for the neuro-developmental shortage associated with CNS infection with CVB.