Protein kinase A activity is required for the budding of constitutive transport vesicles from the trans-Golgi network

We have examined the role played by protein kinase A (PKA) in vesicle-mediated protein transport from the trans-Golgi network (TGN) to the cell surface. In vivo this transport step was inhibited by inhibitors of PKA catalytic subunits (C-PKA) such as the compound known as H89 and a myristoylated form of the inhibitory peptide sequence contained in the thermostable PKA inhibitor. Inhibition by H89 occurred at an early stage during the transfer of vesicular stomatitis virus G glycoprotein from the TGN to the cell surface. Reversal from this inhibition correlated with a transient increase in the number of free coated vesicles in the Golgi area. Vesicle budding from the TGN was studied in vitro using vesicular stomatitis virus-infected, permeabilized cells. Addition to this assay of C-PKA stimulated vesicle release while it was suppressed by PKA inhibitory peptide, H89, and antibody against C-PKA. Furthermore, vesicle release was decreased when PKA-depleted cytosol was used and restored by addition of C-PKA. These results indicate a regulatory role for PKA activity in the production of constitutive transport vesicles from the TGN.

A model of multiplicative neural responses in parietal cortex.

Visual responses of neurons in parietal area 7a are modulated by a combined eye and head position signal in a multiplicative manner. Neurons with multiplicative responses can act as powerful computational elements in neural networks. In the case of parietal cortex, multiplicative gain modulation appears to play a crucial role in the transformation of object locations from retinal to body-centered coordinates. It has proven difficult to uncover single-neuron mechanisms that account for neuronal multiplication. Here we show that multiplicative responses can arise in a network model through population effects. Specifically, neurons in a recurrently connected network with excitatory connections between similarly tuned neurons and inhibitory connections between differently tuned neurons can perform a product operation on additive synaptic inputs. The results suggest that parietal responses may be based on this architecture.