ABSTRACT
Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors and ion channels. PDZ proteins are thought to have a role in defining the cellular distribution of the proteins that interact with them. Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors. Homer is highly divergent from known PDZ proteins and seems to represent a novel family. The Homer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling.
Subject(s)
Carrier Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neuropeptides/metabolism , Receptors, Metabotropic Glutamate/metabolism , Synapses/metabolism , Animals , Binding Sites , Brain/metabolism , Carrier Proteins/chemistry , Carrier Proteins/genetics , Cell Line , Cloning, Molecular , Gene Expression Regulation , Hippocampus/metabolism , Homer Scaffolding Proteins , Humans , Immunoenzyme Techniques , Mice , Molecular Sequence Data , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Neurons/metabolism , Neuropeptides/chemistry , Neuropeptides/genetics , RNA, Messenger/metabolism , Rats , Sequence Deletion , Sequence Homology, Amino Acid , Signal TransductionABSTRACT
The changes in hydrostatic pressure and electrical potentials across vessels in the human vasculature in the presence of a large static magnetic field are estimated to determine the feasibility of in vivo NMR spectroscopy at fields as high as 10 T.A 10-T magnetic field changes the vascular pressure in a model of the human vasculature by less than 0.2%. An exact solution to the magnetohydrodynamic equations describing a conducting fluid flowing transverse to a static magnetic field in a nonconducting, straight, circular tube is used. This solution is compared to an approximate solution that assumes that no magnetic fields are induced in the fluid and that has led previous investigators to predict significant biological effects from static magnetic fields. Experimental results show that the exact solution accurately predicts the magnetohydrodynamic slowing of 15% NaCl flowing transverse to 2.3- and 4.7-T magnetic fields for fluxes below 0.5 liter/min while the approximate solution predicts a much more retarded flow.