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Regulation of monoamine transporters and receptors by lipid microdomains: implications for depression

Neuropsychopharmacologyvolume 43pages21652179 (2018) | Download Citation


Lipid microdomains (“rafts”) are dynamic, nanoscale regions of the plasma membrane enriched in cholesterol and glycosphingolipids, that possess distinctive physicochemical properties including higher order than the surrounding membrane. Lipid microdomain integrity is thought to affect neurotransmitter signaling by regulating membrane-bound protein signaling. Among the proteins potentially affected are monoaminergic receptors and transporters. As dysfunction of monoaminergic neurotransmission is implicated in major depressive disorder and other neuropsychiatric conditions, interactions with lipid microdomains may be of clinical importance. This systematic review evaluates what is known about the molecular relationships of monoamine transporter and receptor regulation to lipid microdomains. The PubMed/MeSH database was searched for original studies published in English through August 2017 concerning relationships between lipid microdomains and serotonin, dopamine and norepinephrine transporters and receptors. Fifty-seven publications were identified and assessed. Strong evidence implicates lipid microdomains in the regulation of serotonin and norepinephrine transporters; serotonin 1A, 2A, 3A, and 7A receptors; and dopamine D1 and β2 adrenergic receptors. Results were conflicting or more complex regarding lipid microdomain associations with the dopamine transporter, D2, D3, and D5 receptors; and negative with respect to β1 adrenergic receptors. Indirect evidence suggests that antidepressants, lipid-lowering drugs, and polyunsaturated fatty acids may exert effects on depression and suicide by altering the lipid milieu, thereby affecting monoaminergic transporter and receptor signaling. The lipid composition of membrane subdomains is involved in localization and trafficking of specific monoaminergic receptors and transporters. Elucidating precise mechanisms whereby lipid microdomains modulate monoamine neurotransmission in clinical contexts can have critical implications for pharmacotherapeutic targeting.

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This study was supported in part by the following grants: K08 MH079033 (PI, MES), NIH R01AT008375 (PI, SRS), NIH 8G12 MD007603 (Area Leader, RES). Dr. JJM receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale (C-SSRS) from the Research Foundation for Mental Hygiene.

Author information

Author notes

    • Joanne J. Liu

    Present address: Chestnut Hill Hospital, Philadelphia, PA, USA

    • Adrienne Hezghia

    Present address: Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA

    • Joshua F. Cenido

    Present address: Department of Psychiatry, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA


  1. Department of Molecular Imaging & Neuropathology, New York State Psychiatric Institute, New York, NY, USA

    • Joanne J. Liu
    • , Adrienne Hezghia
    • , Joshua F. Cenido
    • , J. John Mann
    •  & M. Elizabeth Sublette
  2. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Saame Raza Shaikh
  3. Department of Chemistry and Biochemistry and CUNY Institute for Macromolecular Assemblies, The City College of New York, New York, NY, USA

    • Ruth E. Stark
  4. Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, NY, USA

    • Ruth E. Stark
  5. Department of Psychiatry, Columbia University, New York, NY, USA

    • J. John Mann
    •  & M. Elizabeth Sublette
  6. Department of Radiology, Columbia University, New York, NY, USA

    • J. John Mann


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The authors declare no competing interests.

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Correspondence to M. Elizabeth Sublette.

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