Read Article
Related Articles
Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.
Nguyen LN
et al.
Nature
2014
Brain
Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye
Wong BH
et al.
In: Jiang XC. (eds) Lipid Transfer in Lipoprotein Metabolism and Cardiovascular Disease. Advances in Experimental Medicine and Biology
2020
Brain
The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain
Jia Pei Chan
et al.
PLoS Biology
2018
Brain
Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome
Alicia Guemez-Gamboa 1
et al.
Nature Genetics
2015
Brain
A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome
Vafa Alakbarzade
et al.
Nature Genetics
2015
Brain
The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8 + Memory T Cell Maintenance and Secondary Response to Infection
Ann R Piccirillo
et al.
J Immunol
2019
Brain
Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain
M Lagarde
et al.
Journal of Molecular Neuroscience
2001
Brain
Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain
F Thies
et al.
American Journal of Physiology
1994
Brain
Lysophosphatidylcholine as a carrier of docosahexaenoic acid to target tissues
M Lagarde
et al.
World Rev Nutr Diet
2001
Brain
Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease
Richard D Semba
et al.
Advances in Nutrition
2020
Brain
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis
Benjamin J Andreone
et al.
Neuron
2017
Brain
Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid
Mayssa Hachem
et al.
Molecular Neurobiology
2015
Brain
DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders
Robert K McNamara
et al.
J Nutr.
2010
Brain
Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors
Nicolas G Bazan
et al.
Trends Neurosci
2006
Brain
Preferential transfer of 2-docosahexaenoyl-1-lysophosphatidylcholine through an in vitro blood-brain barrier over unesterified docosahexaenoic acid
N Bernoud
et al.
Journal of Neurochemistry
2002
Brain
Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.
Nguyen LN
et al.
Nature
2014
Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.
Wong BH
et al.
Journal of Biological Chemistry
2016
Lipase Treatment of Dietary Krill Oil, but Not Fish Oil, Enables Enrichment of Brain Eicosapentaenoic Acid and Docosahexaenoic Acid.
Yalagala PCR
et al.
Molecular Nutrition & Food Research
2020
Efficient Enrichment of Retinal DHA with Dietary Lysophosphatidylcholine-DHA: Potential Application for Retinopathies.
Sugasini D
et al.
Nutrients
2020
Disrupted Blood-Retina Lysophosphatidylcholine Transport Impairs Photoreceptor Health But Not Visual Signal Transduction
Ekaterina S Lobanova
et al.
The Journal of Neuroscience
2019
Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice
Dhavamani Sugasini
et al.
Scientific Reports
2017
Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye
Wong BH
et al.
In: Jiang XC. (eds) Lipid Transfer in Lipoprotein Metabolism and Cardiovascular Disease. Advances in Experimental Medicine and Biology
2020
Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol
Dhavamani Sugasini
et al.
The Journal of Nutritional Biochemistry
2019
The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain
Jia Pei Chan
et al.
PLoS Biology
2018
Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: potential treatment for depression
Poorna C. R. Yalagala
et al.
Journal of Lipid Research
2019
Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome
Alicia Guemez-Gamboa 1
et al.
Nature Genetics
2015
A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome
Vafa Alakbarzade
et al.
Nature Genetics
2015
Insights into major facilitator superfamily domain-contaning protein-2a (Mfsd2a) in physiology and pathophysiology. What do we know so far?
Eser Ocak P
et al.
Journal of Neuroscience Research
2020
Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy
María Sánchez-Campillo
et al.
Frontiers in Endocrinology
2020
The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8 + Memory T Cell Maintenance and Secondary Response to Infection
Ann R Piccirillo
et al.
J Immunol
2019
Homozygous mutation in MFSD2A, encoding a lysolipid transporter for docosahexanoic acid, is associated with microcephaly and hypomyelination
Tamar Harel
et al.
Neurogenetics
2018
Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain
M Lagarde
et al.
Journal of Molecular Neuroscience
2001
The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina
John Paul SanGiovanni
et al.
Prog Retin Eye Res.
2005
Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain
F Thies
et al.
American Journal of Physiology
1994
Lysophosphatidylcholine as a carrier of docosahexaenoic acid to target tissues
M Lagarde
et al.
World Rev Nutr Diet
2001
Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier
Zhongxiao Wang
et al.
Science Advances
2020
Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease
Richard D Semba
et al.
Advances in Nutrition
2020
Omega-3 PUFA metabolism and brain modifications during aging
Hillary Chappus-McCendie
et al.
Prog Neuropsychopharmacol Biol Psychiatry
2019
Carriers of an apolipoprotein E epsilon 4 allele are more vulnerable to a dietary deficiency in omega-3 fatty acids and cognitive decline
Tanya Gwendolyn Nock
et al.
Biochim Biophys Acta Mol Cell Biol Lipids.
2017
Docosahexaenoic acid prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice
Raphaël Chouinard-Watkins
et al.
Neurobiology of Aging
2017
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis
Benjamin J Andreone
et al.
Neuron
2017
Gradual Suppression of Transcytosis Governs Functional Blood-Retinal Barrier Formation
Brian Wai Chow
et al.
Neuron
2017
Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases
Amanda Lo Van
et al.
Biochimie
2016
Mfsd2a-based pharmacological strategies for drug delivery across the blood-brain barrier
Jing-Zhang Wang
et al.
Pharmachological Research
2016
The Cellular and Molecular Landscapes of the Developing Human Central Nervous System
John C Silbereis
et al.
Neuron
2016
Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid
Mayssa Hachem
et al.
Molecular Neurobiology
2015
Blood-brain barrier: a dual life of MFSD2A?
Zhao Z
et al.
Neuron
2014
Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations
Philippe Guesnet
et al.
Biochimie
2011
DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders
Robert K McNamara
et al.
J Nutr.
2010
The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity
Robert K McNamara
et al.
Prostaglandins Leukot Essent Fatty Acids
2008
Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors
Nicolas G Bazan
et al.
Trends Neurosci
2006
The role of essential fatty acids in development
William C Heird
et al.
Annu Rev Nutr
2005
Preferential transfer of 2-docosahexaenoyl-1-lysophosphatidylcholine through an in vitro blood-brain barrier over unesterified docosahexaenoic acid
N Bernoud
et al.
Journal of Neurochemistry
2002
Chemistry and metabolism of lipids in the vertebrate retina
S J Fliesler
et al.
Prog Lipid Res
1983
The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys
D R Illingworth, O W Portman
et al.
Biochem J .
1972
Visual cells and the concept of renewal
Young R W
et al.
Investigative Ophthalmology & Visual Science
1976
Maternal DHA and the development of attention in infancy and toddlerhood
John Colombo
et al.
Child Dev.
2004
1. Adv Exp Med Biol. 2020;1276:223-234. doi: 10.1007/978-981-15-6082-8_14.

Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye

March 4, 2016
Wong BH(1), Silver DL(2).

(1)Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore.

(2)Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore. David.Silver@Duke-NUS.edu.sg.

Abstract

Lipids and essential fatty acids are required for normal brain development and continued photoreceptor membrane biogenesis for the maintenance of vision. The blood-brain barrier and blood-eye barriers prohibit the free diffusion of solutes into the brain and eye so that transporter-mediated uptake predominates at these barriers. The major facilitator superfamily of transporters constitutes one of the largest families of facilitative transporters across all domains of life. A unique family member, major facilitator superfamily domain containing 2a (Mfsd2a) is a lysophosphatidylcholine (LPC) transporter expressed at the blood-brain and blood-retinal barriers and demonstrated to be the major pathway for brain and eye accretion of docosahexaenoic acid (DHA) as an LPC. In addition to LPC-DHA, Mfsd2a can transport other LPCs containing mono- and polyunsaturated fatty acids. Mfsd2a deficiency in mouse and humans results in severe microcephaly, underscoring the importance of LPC transport in brain development. Beyond its role in brain development, LPC-DHA uptake in the brain and eye negatively regulates de novo lipogenesis. This review focuses on the current understanding of the physiological roles of Mfsd2a in the brain and eye and the proposed transport mechanism of Mfsd2a.

Keywords
Brain
Eye
Lipid transfer activity
Lysolipids
Major facilitator superfamily (MFS)
Major facilitator superfamily domain containing 2a (Mfsd2a)
RELATED