Research Spotlight: PMP2/FABP8 Induces PI(4,5)P2-Dependent Transbilayer Reorganization of Sphingomyelin in the Plasma Membrane

Posted on December 14, 2021


Dec Research Spotlight 2 Image

We love to read research results published by our valued customers, and we love to share those results with you! Toshihide Kobayashi, National Center for Scientific Research/University of Strasbourg, said this about our lipids “We cannot publish these results without Avanti lipids. Thank you very much for the high-quality lipids.” Thank you, Toshihide, for being a loyal Avanti customer! Okay, let’s dive into the fantastic research that Toshihide has been doing!

The question: How does sphingomyelin (SM) move in the transbilayer? And how does it affect membrane organization?

Toshihide’s work answers these questions. But before we get to the answers, it is important to understand a little information regarding this question’s importance. There is known asymmetry of lipids in the plasma membrane (PM). Phosphatidylcholine (PC) is primarily located in the outer leaflet while phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and phosphatidylinositol 4,5-bisphosphatee (PI(4,5)P2) are primarily located in the inner leaflet. How the asymmetrical distribution of these lipids is maintained is not fully understood but is postulated to involve flippases, floppases, and scramblases.

Mammalian cells are comprised of nearly 10% SM. Bulk SM is synthesized on the luminal side of the Golgi apparatus and transported to the outer leaflet by SM synthase 1, where local SM is synthesized on the extracellular side by SM synthase 2. So, originally, the asymmetrical distribution of SM in the plasma membrane is a function of SM synthases. But how is this maintained?

Based on their findings, Toshihide and his research group suggest that peripheral myelin protein 2 (PMP2) controls the transbilayer movement of SM. Here is a list of the key results from this study: (1) SM moves from the outer leaflet to the inner leaflet, (2) PMP2 is responsible for the endocytosis-independent transport of fluorescent SM from the outer to the inner leaflet of the PM, (3) PMP2 induces the tubulation of model membranes, and (4) pathogenic mutant PMP2 binds more strongly to PI(4,5)P2.

In addition to proving PMP2’s involvement in the transbilayer movement of SM in the PM, this study also revealed several other proteins involved in membrane trafficking (GGA1, RAB6A, and ASAP2). A future study might be able to show if these proteins are specifically involved in the transbilayer movement of SM in the membranes of intracellular organelles. Number 4 from the list above is an important finding from this study. The pathogenic mutant PMP2, the causative protein of Charcot-Marie-Tooth (CMT) Disease, was shown to bind more strongly to PI(4,5)P2 and to sequester PI(4,5)P2 in HeLa cells. The pathological and physiological hallmark of CMT disease is demyelination. PI(4,5)P2 is required for several crucial steps in the myelination process. The higher-binding affinity and sequestering of PI(4,5)P2 by the pathogenic mutant PMP2 would explain why demyelination occurs in patients with CMT Disease.

Fascinating research and findings from Toshihide! We are grateful for you as a customer and member of the lipid research community. Toshihide’s research took advantage of several lipids provided by Avanti shown in the table below. To navigate to a product’s page, click on its name or product number! If you’re interested in another lipid in the same category as one listed below, click on the category to scroll through similar lipids that we offer! And if you still can’t find what you’re looking for, contact us for a custom synthesis quote. To read Toshihide’s full research article published in Cell Reports, click HERE!

Image Credit: Original Research Publication

Long Name

Short Name

Product Number

Product Category

sphingomyelin

Brain SM

860062

Sphingolipids

1,2-dioleoyl-sn-glycero-3-phosphocholine

DOPC

850375

PC and LPC

1-palmitoyl-2-oleoyl-sn-glycero-3-

phosphoethanolamine

16:0-18:1 PE

850757

PE and LPE

l-a-phosphatidylinositol

Liver PI

840042

PI, PIP, LPI

1,2-dioleoyl-sn-glycero-3-phospho-(1’-myoinositol-

4’,50-bisphosphate)

18:1 PI(4,5)P2

850155

PI, PIP, LPI

l-a-phosphatidylserine

Brain PS

840032

PS and LPS

Ceramide

Cer (Brain)

860052

Sphingolipids

Total Cerebrosides

Cerebrosides (Brain)

131303

Sphingolipids

N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]

hexanoyl]-sphingosine-1-phosphocholine

C6-NBD-SM

810218

Fluorescent Lipids

1-oleoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)

amino]dodecanoyl]-sn-glycero-3-

phosphoethanolamine

C12-NBD-PE

810156

Fluorescent Lipids

N-(lissamine rhodamine B sulfonyl)-

dioleoylphosphatidylethanolamine

N-LRh-PE

810150

Fluorescent Lipids

1,2-dioleoyl-sn-glycero-3-phospho-(1’-myoinositol-

30,50-bisphosphate)

18:1 PI(3,5)P2

850154

PI, PIP, LPI

Mini-Extruder

Mini-Extruder

610023

Equipment