![]() The intracellular antagonism and intercellular communication are both important for establishing and maintaining planar polarity along the entire tissue. These core PCP signaling components not only form complexes that are localized asymmetrically and antagonize each other within the same cell but also form asymmetric intercellular complexes between neighboring cells. The PCP pathway, establishing tissue and cell polarity along the plane of the tissue, is highly conserved from Drosophila to mammals, involving six core components, including Frizzled (Fzd), Flamingo (named Celsrs in vertebrates), Van Gogh (named Vangls in vertebrates), Dishevelled (Dvl), Prickle, and Diego. The planar cell polarity (PCP) is a promising candidate for such a common pathway ( 13). Therefore, the signaling mechanism that directly assembles glutamatergic synapses has been missing, leading to the question whether a common pathway even exists. They are typically not essential for glutamatergic synapse formation, because synapse formation is either not affected or only mildly affected in vivo even in straight knockouts ( 9, 11, 12). ![]() Synaptic adhesion molecules have been studied extensively and are important for the function and, in some cases, the specificity of synaptic connections ( 9, 10). ![]() However, whether all glutamatergic synapses are assembled by a common signaling mechanism, operating locally in the synapses, or by many different alternative pathways is not clear. Extensive efforts have been made to study how this exquisite structure is assembled and regulated, and many signaling cascades, such as neurotrophin signaling, have been found to affect synapse formation, especially dendritic spine formation ( 8). ![]() Despite the tremendous diversity of glutamatergic synapses in terms of their connectivity, morphology, and electrophysiological properties, they have a common structural design, typically with a prominent postsynaptic density, dendritic spine, and highly organized presynaptic active zone ( 4– 7). Glutamatergic synapses are the main excitatory synapses in the mammalian brain, and their normal formation and function are critical to brain function ( 1– 5). In summary, the PCP components regulate the assembly and maintenance of a large number of glutamatergic synapses and specify the direction of synaptic transmission. Coculture experiments show that the asymmetric PCP complexes can determine the presynaptic and postsynaptic polarity. ![]() Prickle2 promotes synapse formation by antagonizing Vangl2 and stabilizing the intercellular complex of the planar cell polarity (PCP) components, whereas Prickle2 E8Q fails to do so. PSD-95–positive glutamatergic synapses in the hippocampus of Prickle2 E8Q/E8Q mice were reduced by 50% at postnatal day 14. Prickle1 and Prickle2 double knockout in adulthood lead to the disassembly of 70 to 80% of the postsynaptic-density(PSD)-95–positive glutamatergic synapses. We show here that knocking out Prickle1 and Prickle2 reduced the formation of the PSD-95–positive glutamatergic synapses in the hippocampus and medial prefrontal cortex in postnatal development by 70–80%. Whether there exists a common signaling mechanism that assembles all glutamatergic synapses is unknown. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |