Jonathan Cohen

Jonathan Cohen, PhD

Bullard Professor of Neurobiology, Emeritus

Ion Channel and Neurotransmitter Biology

Neurons communicate with each other through the release of neurotransmitter molecules such as glutamate, GABA, acetylcholine, dopamine, serotonin, etc. at synapses. When a neurotransmitter binds to its receptor on the membrane of a neuron, it opens up ion channels that result in neuronal excitation or inhibition. Better understanding how this process works has many implications, both for basic neuroscience and our understanding of nervous system disorders.

The Cohen lab focuses on molecular studies of receptors for GABA, the major inhibitory neurotransmitter in the brain, and acetylcholine, an excitatory neurotransmitter in many brain regions and at nerve-muscle contacts. GABAA receptors (GABAAR) are the targets for many important drugs, including antiepileptics, sedatives and general anesthetics. One current project in the lab is focused on determining the diversity of general anesthetic biding sites in GABAARs, which will provide a basis for the development of anesthetics with fewer undesirable side effects.

Nicotinic acetylcholine receptors (nAChR), which are the site of binding of nicotine, are involved in the regulation of sleep, attention, learning, and memory. Dysfunctions of nAChRs are implicated in disorders including Alzheimer’s and Parkinson’s, and drugs that target nAChRs have potential uses in the treatment of these conditions as well as nicotine addiction. nAChRs on skeletal muscle mediate neural control of muscle contraction, and they are the receptors that are destroyed in an autoimmune disease, myasthenia gravis.  Currently the Cohen lab is studying the mechanisms of novel classes of drugs that act as enhancers of brain or muscle nAChRs.

Publications View
Spatial structure of the M3 transmembrane segment of the nicotinic acetylcholine receptor alpha subunit.
Authors: Authors: Lugovskoy AA, Maslennikov IV, Utkin YN, Tsetlin VI, Cohen JB, Arseniev AS.
Eur J Biochem
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Probing the structure of the nicotinic acetylcholine receptor ion channel with the uncharged photoactivable compound -3H-diazofluorene.
Authors: Authors: Blanton MP, Dangott LJ, Raja SK, Lala AK, Cohen JB.
J Biol Chem
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Mechanism of nicotinic acetylcholine receptor cluster formation by rapsyn.
Authors: Authors: Ramarao MK, Cohen JB.
Proc Natl Acad Sci U S A
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Identification of tryptophan 55 as the primary site of [3H]nicotine photoincorporation in the gamma-subunit of the Torpedo nicotinic acetylcholine receptor.
Authors: Authors: Chiara DC, Middleton RE, Cohen JB.
FEBS Lett
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Identification of amino acids contributing to high and low affinity d-tubocurarine sites in the Torpedo nicotinic acetylcholine receptor.
Authors: Authors: Chiara DC, Cohen JB.
J Biol Chem
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Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane.
Authors: Authors: Sadoulet-Puccio HM, Khurana TS, Cohen JB, Kunkel LM.
Hum Mol Genet
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Agonist-induced photoincorporation of a p-benzoylphenylalanine derivative of substance P into membrane-spanning region 2 of the Torpedo nicotinic acetylcholine receptor delta subunit.
Authors: Authors: Blanton MP, Li YM, Stimson ER, Maggio JE, Cohen JB.
Mol Pharmacol
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Identifying the lipid-protein interface of the Torpedo nicotinic acetylcholine receptor: secondary structure implications.
Authors: Authors: Blanton MP, Cohen JB.
Biochemistry
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Agonist-induced changes in the structure of the acetylcholine receptor M2 regions revealed by photoincorporation of an uncharged nicotinic noncompetitive antagonist.
Authors: Authors: White BH, Cohen JB.
J Biol Chem
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Structure of the noncompetitive antagonist-binding site of the Torpedo nicotinic acetylcholine receptor. [3H]meproadifen mustard reacts selectively with alpha-subunit Glu-262.
Authors: Authors: Pedersen SE, Sharp SD, Liu WS, Cohen JB.
J Biol Chem
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