A Perspective : Active Role of Lipids in Neurotransmitter Dynamics

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Postila , P A & Róg , T 2020 , ' A Perspective : Active Role of Lipids in Neurotransmitter Dynamics ' , Molecular Neurobiology , vol. 57 , no. 2 , pp. 910-925 . https://doi.org/10.1007/s12035-019-01775-7

Title: A Perspective : Active Role of Lipids in Neurotransmitter Dynamics
Author: Postila, Pekka A.; Róg, Tomasz
Contributor organization: Department of Physics
Date: 2020-02
Language: eng
Number of pages: 16
Belongs to series: Molecular Neurobiology
ISSN: 1559-1182
DOI: https://doi.org/10.1007/s12035-019-01775-7
URI: http://hdl.handle.net/10138/312179
Abstract: Synaptic neurotransmission is generally considered as a function of membrane-embedded receptors and ion channels in response to the neurotransmitter (NT) release and binding. This perspective aims to widen the protein-centric view by including another vital component—the synaptic membrane—in the discussion. A vast set of atomistic molecular dynamics simulations and biophysical experiments indicate that NTs are divided into membrane-binding and membrane-nonbinding categories. The binary choice takes place at the water-membrane interface and follows closely the positioning of the receptors’ binding sites in relation to the membrane. Accordingly, when a lipophilic NT is on route to a membrane-buried binding site, it adheres on the membrane and, then, travels along its plane towards the receptor. In contrast, lipophobic NTs, which are destined to bind into receptors with extracellular binding sites, prefer the water phase. This membrane-based sorting splits the neurotransmission into membrane-independent and membrane-dependent mechanisms and should make the NT binding into the receptors more efficient than random diffusion would allow. The potential implications and notable exceptions to the mechanisms are discussed here. Importantly, maintaining specific membrane lipid compositions (MLCs) at the synapses, especially regarding anionic lipids, affect the level of NT-membrane association. These effects provide a plausible link between the MLC imbalances and neurological diseases such as depression or Parkinson’s disease. Moreover, the membrane plays a vital role in other phases of the NT life cycle, including storage and release from the synaptic vesicles, transport from the synaptic cleft, as well as their synthesis and degradation.
Subject: CRYSTAL-STRUCTURES
DOPAMINE TRANSPORTER
FREE-ENERGY PROFILE
HYDROGEN-SULFIDE
MEMBRANE-LIPIDS
Membrane lipid composition (MLC)
Membrane-based sorting
Molecular dynamics (MD)
NERVOUS-SYSTEM
NITRIC-OXIDE DIFFUSION
Neurotransmitter
PLASMA-MEMBRANE
SYNAPTIC VESICLE
Synaptic neurotransmission
Synaptic receptor
X-RAY STRUCTURES
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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