operate. Because these proteins are directly respon- 
sible for the ability of nerve cells to generate electri- 
cal signals, they lie at the molecular foundations of 
the nervous system. Current research by this group 
is aimed at the structure and function of potassium- 
specific channels, the purification of chloride- 
specific channels, and the interaction of certain 
channels with peptide neurotoxins. 
The research of Investigator Roger Y. Tsien, Ph.D. 
(University of California, San Diego) and his col- 
leagues focuses on intracellular signal transduction 
and nev^' molecules to probe these biochemical 
mechanisms. Many hormones and neurotransmitters 
influence gene expression through the transloca- 
tion of the catalytic subunit of cAMP-dependent 
protein kinase into the nucleus. This translocation 
was surprisingly found to be independent of kinase 
activity and mediated by passive diffusion. Prelimi- 
nary evidence was found for a novel membrane- 
permeant messenger mediating calcium influx, 
whereas another messenger previously thought to 
have that role seems to depress intracellular cal- 
cium or uncouple it from downstream physiological 
functions. New molecules were devised for photo- 
chemically controlled release of intracellular cal- 
cium and the intercellular messenger nitric oxide. 
Transmembrane signal transduction plays a key 
role in cellular physiology, growth, development, 
and differentiation. The most widespread trans- 
membrane signaling system involves a superfamily 
of related G proteins and G protein-coupled mem- 
brane receptors. The laboratory of Assistant Investi- 
gator Thomas P. Sakmar, M.D. (Rockefeller Univer- 
sity) employs the visual proteins transducin and 
rhodopsin as a model system for structure-function 
studies on the molecular mechanism of transmem- 
brane signaling. The key approach has been to re- 
constitute heterologously expressed rhodopsin and 
transducin in vitro under defined conditions and to 
use biochemical and biophysical methods to probe 
site-directed mutants. For example, ultraviolet- 
visible spectroscopy of mutant pigments has helped 
to identify specific amino acids that determine the 
spectral properties of rhodopsin and the green and 
red human color pigments. The question of how a 
photochemical signal is transmitted from the core of 
rhodopsin to its surface where transducin becomes 
activated has also been addressed using a method 
that allows measurements of rhodopsin-transducin 
interactions by intrinsic fluorescence. Mixtures of 
rhodopsin and transducin can be assayed, and the 
effects of specific mutations can be evaluated. These 
studies may lead to a better understanding at a mo- 
lecular level of how receptors activate their respec- 
tive G proteins. 
Visual sensory cells have characteristic responses 
that include photo-induced excitation followed by 
recovery and adaptation. Associate Investigator 
James B. Hurley, Ph.D. (University of Washington) is 
exploring the fundamental mechanisms of visual 
phototransduction. The roles of vertebrate photore- 
ceptor proteins such as transducin and recoverin in 
recovery and adaptation were elucidated by a combi- 
nation of genetic and biochemical investigations. A 
unique type of G protein subunit was identified in 
Drosophila photoreceptors, and it was shown to 
play a critical role in Drosophila phototransduc- 
tion. The aim of these studies is to understand the 
molecular mechanisms that generate and regulate 
the primary visual response. 
In the past year. Investigator King-Wai Yau, Ph.D. 
(Johns Hopkins University) and his colleagues con- 
tinued to focus on the phototransduction process in 
the retina. A major finding is that the cGMP-gated 
cation channel that mediates this process appears to 
be a hetero-oligomer, rather than a homo-oligomer 
as had previously been thought. They have cloned 
an apparently new species of this channel subunit 
that by itself is unable to form a functional channel 
but when coexpressed with another subunit confers 
the flickering channel kinetics that are characteris- 
tics of the native channel. 
Recent research has uncovered the existence of a 
specialized pathway in the cerebral cortex that ap- 
pears to process information about visual motion. 
Signals about visual motion form the foundation of 
many aspects of higher-order visual analysis, and the 
laboratory of Investigator J. Anthony Movshon, Ph.D. 
(New York University) has been exploring several 
ways in which these signals support perceptual de- 
cisions and visuomotor behavior. By combining 
electrophysiological recording with perceptual ex- 
periments in awake trained monkeys, the group has 
shown that despite an available large pool of neu- 
rons in the cortical motion pathway, the informa- 
tion carried by small numbers is sufficient to sup- 
port perceptual performance. This finding suggests 
that it may be neither necessary nor desirable for the 
brain to pool large numbers of distributed neuronal 
signals to arrive at perceptual decisions. Signals 
carried by these same cortical neurons are thought 
to provide information to the motor system for the 
generation of smooth pursuit eye movements, used 
by primates to stabilize the retinal image of attended 
moving visual targets. Analysis of the dynamics of 
these rapid and precise movements suggests that vi- 
sual motion signals may carry information about tar- 
get speed, direction, and acceleration. 
The research in the laboratory of Investigator 
TerrenceJ. Sejnowski, Ph.D. (Salk Institute) onmod- 
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