zation. These experiments should directly reveal 
the time course of calcium influx and release within 
the photoreceptor during the light-activated 
response. 
ninaA and Related Cyclophilins 
The ninaA gene product is a photoreceptor- 
specific cyclophilin that is required for proper 
rhodopsin biogenesis. ninaA flies have 5-10% of v^ild- 
type levels of Rhl rhodopsin in their Rl-6 photore- 
ceptor cells and yet have wild-type levels of the Rhl 
mRNA. Cyclophilins are a conserved family of 
peptidyl-prolyl cis- trans isomerases that have been 
implicated in intracellular protein trafficking and 
folding and are believed to mediate the effects of the 
powerful immunosuppressing drug cyclosporin A. 
To gain insight into the role of cyclophilins, the 
laboratory carried out a genetic screen designed to 
identify functionally important regions in the ninaA 
protein. More than 700,000 mutagenized chromo- 
somes were screened for a visible ninaA phenotype, 
and 70 independent mutations in ninaA were iso- 
lated and characterized. This screen, based on a 
rhodopsin-dependent phenotype and unbiased in its 
requirement for a defined biochemical activity of 
ninaA, has provided significant insight into the 
structure/function relationships important to the 
natural cellular function of a cyclophilin. Remark- 
ably, most of the changes mapped to or near the 
/S-barrel face of cyclophilin that appears to be in- 
volved in cyclosporin A binding and prolyl- 
isomerase substrate binding. These results provide 
the strongest argument to date that the functionally 
relevant region of the molecule, in vivo, corre- 
sponds to and overlaps with the peptidyl-prolyl 
substrate-binding site. 
In a related set of studies, the gene encoding the 
Drosophila homologue of the abundant, cytosolic 
form of human cyclophilin was cloned, and several 
screening strategies are being employed to isolate 
mutations in this locus. The generation of cyclophi- 
lin mutants in Drosophila should greatly extend 
knowledge of the biological role of this class of pro- 
tein and provide a useful tool for the genetic identi- 
fication of their intracellular targets. 
The work described above was supported by 
grants from the National Eye Institute, National Insti- 
tutes of Health. 
Mutants Insensitive to the Bat 
of an Eyelash 
Dr. Zuker's laboratory has recently extended its 
studies into a new aspect of sensory transduction: a 
search for the molecular basis of mechanotransduc- 
tion, the conversion of mechanical stimuli into neu- 
ronal signals that underlies the senses of touch, 
hearing, and balance. The electrophysiology and 
biophysics of some mechanosensory organs have 
been described in detail, but, in contrast to the or- 
gans of sight, taste, and smell, nothing is known of 
the molecular identity of their transducers. 
Dr. Zuker and his colleagues are identifying genes 
that encode mechanosensory components in Dro- 
sophila by isolating mutations that affect touch- 
induced behavior. In contrast to defects in photore- 
ception, a complete loss of mechanosensation 
would probably kill an adult fly. Therefore this 
screen relied on behavioral defects in the larval 
stages: specifically, a touch-evoked turning and 
withdrawal of the larva away from a gentle touch 
with an eyelash. A screen of the X chromosome — 
20% of the Drosophila genome — has yielded 40 
mutations with defects in this behavior, ranging 
from somewhat uncoordinated movement to com- 
plete mechanoinsensitivity. A preliminary genetic 
mapping and sorting shows that at least four genes 
have been hit multiple times. The mutant lines are 
now being examined for defects in larval and adult 
anatomy, behavior, and physiology. 
Dr. Zuker is also Associate Professor of Biology 
and of Neurosciences at the University of Califor- 
nia School of Medicine, San Diego. 
Articles 
Cassill, J.A., Whitney, M., Joazeiro, C.A.P., Becker, 
A., and Zuker, C.S. 1991. Isolation of Drosoph- 
ila genes encoding G protein-coupled receptor 
kinases. Proc Natl Acad Sci USA 88:11067- 
11070. 
Colley, N.J., Baker, E.K., Stamnes, M.A., and Zuker, 
C.S. 1991. The cyclophilin homolog ninaA is re- 
quired in the secretory pathway. Cell 67:255- 
263. 
Ranganathan, R., Harris, G.L., Stevens, C.F., and 
Zuker, C.S. 1 99 1 . A Drosophila mutant defective 
in extracellular calcium-dependent photorecep- 
tor deactivation and rapid desensitization. Nature 
354:230-232. 
Ranganathan, R., Harris, W.A., and Zuker, C.S. 
1991. The molecular genetics of invertebrate 
phototransduction. Trends Neurosci 14:486- 
493. 
Smith, D.P., Ranganathan, R., Hardy, R.W., Marx, J., 
Tsuchida, T., and Zuker, C.S. 1991. Photorecep- 
tor deactivation and retinal degeneration me- 
diated by a photoreceptor-specific protein kinase 
C. Science 254:1478-1484. 
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