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Murray Sherman S.,University of Chicago | Guillery R.W.,Medical Research Council Anatomical Neuropharmacology Unit
Journal of Neurophysiology | Year: 2011

Essentially all cortical areas receive thalamic inputs and send outputs to lower motor centers. Cortical areas communicate with each other by means of direct corticocortical and corticothalamocortical pathways, often organized in parallel. We distinguish these functionally, stressing that the transthalamic pathways are class 1 (formerly known as "driver") pathways capable of transmitting information, whereas the direct pathways vary, being either class 2 (formerly known as "modulator") or class 1. The transthalamic pathways provide a thalamic gate that can be open or closed (and otherwise more subtly modulated), and these inputs to the thalamus are generally branches of axons with motor functions. Thus the transthalamic corticocortical pathways that can be gated carry information about the cortical processing in one cortical area and also about the motor instructions currently being issued from that area and copied to other cortical areas. © 2011 the American Physiological Society.

Perestenko P.V.,Medical Research Council Anatomical Neuropharmacology Unit | Pooler A.M.,Medical Research Council Anatomical Neuropharmacology Unit | Pooler A.M.,Institute of Psychiatry | Noorbakhshnia M.,Medical Research Council Anatomical Neuropharmacology Unit | And 5 more authors.
FEBS Journal | Year: 2010

The copines are a family of C2- and von Willebrand factor A-domain-containing proteins that have been proposed to respond to increases in intracellular calcium by translocating to the plasma membrane. The copines have been reported to interact with a range of cell signalling and cytoskeletal proteins, which may therefore be targeted to the membrane following increases in cellular calcium. However, neither the function of the copines, nor their actual movement to the plasma membrane, has been fully established in mammalian cells. Here, we show that copines-1, -2, -3, -6 and -7 respond differently to a methacholine-evoked intracellular increase in calcium in human embryonic kidney cell line-293 cells, and that their membrane association requires different levels of intracellular calcium. We demonstrate that two of these copines associate with different intracellular vesicles following calcium entry into cells, and identify a novel conserved amino acid sequence that is required for their membrane translocation in living cells. Our data show that the von Willebrand factor A-domain of the copines modulates their calcium sensitivity and intracellular targeting. Together, these findings suggest a different set of roles for the members of this protein family in mediating calcium-dependent processes in mammalian cells. © 2010 FEBS.

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