Saturday, 24th August 2019

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PIE Council

General Council Members XII

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Maurice Israël: Born in Alexandria (1938), I studied medicine, then biochemistry, in Paris; learned research with R. Couteaux, in his laboratory Rue Cuvier; then with VP. Whittaker, in Cambridge-Babraham-Hall; Sir John Gaddum was director of this leading institute in 1964.

My first work: The sternomastoid muscle has a localized innervated zone, I confirmed that acetylcholinesterase was in postsynaptic folds, and for the first time, showed that acetylcholine and cholineacetyltransferase were in the nerve. I used, for measuring ACh the leech dorsal muscle, adapted to Gaddum’s-microbath and the tetraphenylborate procedure for cholineacetyltransferase, studied with F. Fonnum (Oslo).

In Whittaker’s, I purified giant-mossy-fiber glutamatergic synaptosomes.

My main work: Purification of Torpedo Electric organ synaptic vesicles demonstrated that they contained most of the acetylcholine (1968) appreciated by Sir Bernard Katz, he won the 1970 Nobel Prize, for quantal transmission and vesicular theory.  Synaptic vesicle traffic-proteins led again to 2013 Nobel.

Nonconsensual work: with RM. Marchbanks, I studied cytosolic ACh; when Y. Dunant joined my Salpêtriere group, we showed the unexpected release of cytosolic acetylcholine upon stimulation, while vesicles remained unchanged. The work was continued in L. Tauc’s institute (Gif-sur-Yvette).

Essential works: Purification of Torpedo electric organ synaptosomes, then Acetylcholine- chemiluminescent-cholineoxidase assay (Israël, Lesbats 1980). They allowed monitoring cytosolic acetylcholine changes and intramembrane particle variations, counted in freeze fracture replicas; in parallel to electrical activity. A long lasting collaboration with Y. Dunant, pointed at a protein ensuring transmitter release: Mediatophore it was purified, reconstituted in membranes, cloned. When J. Falk approached “myoballs” from mediatophore-transfected cells, acetylcholine quanta were recorded.

Other works
- Retroinhibition of acetylcholine release by released adenosine triphosphate
- Calcium uptake by synaptic vesicles prevents release desensitization
- Chemiluminescent assays for five transmitters, release of glutamate from mossy fiber synaptosomes , comparison with other transmitters.

In my lab
- Vesicular transporter was cloned, it is embedded in the cholineacetyltransferase gene
- Genetic disease treatment by re-expressing silent fetal-homolog genes: Utrophine replaces mutated dystrophine.

CNRS Director, I retired in 2003; got interested in Cancer metabolism, deduced that metabolic-rewiring came from a pancreatic GABA failure (2010).  Anti-cancer drugs were proposed.

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