Jaffe asks Nirenberg about his latest research with acetylcholine and neuroblastoma. He also provides details from his own
research, suggests additional research possibilities, and offers the prospect of future collaborations.
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1971-02-21 (February 21, 1971)
Jaffe, M. J.
Nirenberg, Marshall W.
Courtesy of Marshall W. Nirenberg.
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Thank you for sending me a reprint of "Acetylcholinesterase in neuroblastoma cells". I am particularly interested
to see the inverse relationship between AChE activity and cell division. My laboratory is concerned with the problem of sensory
physiology, and we have been studying several developmental systems that also have interesting electrical properties. I have
shown that phytochrome, the light receptor that mediates all photoperiodic phenomena in higher plants, is itself regulated
by ACh (as in the enclosed reprint). Since ACh has now been implicated in several animal systems as a developmental regulator
(e.g. Gustafson and Toneby, Exp. Cell Res. 62: 102-117 (1970)), I am curious as to whether or not you have measured the ACh
concentration in your cells when they are or are not. As you can see in figures 6 and 7 of the enclosed reprint, the ACh
levels are especially high in buds and secondary roots, the only organs in which cell division may be said to be actively
occurring. Whether or not this is due to decreased AChE activity, or increased acetylcholine synthesis remains to be seen.
We have just now succeeded in demonstrating true AChE activity, and are beginning to look for choline acetyltransferase activity
in the secondary roots.
Although ACh is best known for its role as a neuro-transmitter, it seems to be found in all living cells including prokaryotic
cells. In addition to its control of membrane permeability (Table VI, and much animal work), might it not be that its primary
function evolved to regulate cell division, and that its role in nerves, etc. is, in fact, regressive, with the advent of
an auxiliary system to protect against division?
I hope ultimately to be able to explain the mode of action of ACh in our system, and have taken the approach of studying its
interaction with each organelle in turn. In addition to the obvious effect of ACh on the cell membrane, we have also demonstrated
a clear cut and unexpected type of mitochondria regulation, and have preliminary evidence that the nuclear envelope is strongly
effected by ACh. If you are interested, I shall send you reprints of those papers when they appear.