A2 Review article, Literature review, Systematic review
A Perspective : Active Role of Lipids in Neurotransmitter Dynamics (2020)


Postila, P. A., & Róg, T. (2020). A Perspective : Active Role of Lipids in Neurotransmitter Dynamics. Molecular Neurobiology, 57(2), 910-925. https://doi.org/10.1007/s12035-019-01775-7


JYU authors or editors


Publication details

All authors or editorsPostila, Pekka A.; Róg, Tomasz

Journal or seriesMolecular Neurobiology

ISSN0893-7648

eISSN1559-1182

Publication year2020

Volume57

Issue number2

Pages range910-925

PublisherSpringer

Publication countryGermany

Publication languageEnglish

DOIhttps://doi.org/10.1007/s12035-019-01775-7

Publication open accessOpenly available

Publication channel open accessPartially open access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/66235


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.


Keywordsmolecular neurobiologysynapsestransmitters (chemical compounds)cell membraneslipidsmolecular dynamics

Free keywordssynaptic neurotransmission; neurotransmitter; synaptic receptor; membrane-based sorting; molecular dynamics (MD); membrane lipid composition (MLC)


Contributing organizations


Ministry reportingYes

Reporting Year2020

JUFO rating1


Last updated on 2024-03-04 at 21:45