Rafting on the Plasma Membrane: Lipid Rafts in Signaling and Disease

Isik, Ozlem Aybuke; Cizmecioglu, Onur

doi:10.1007/5584_2022_759

Cited by 6 publications

(1 citation statement)

References 208 publications

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“…One plausible explanation for how sphingolipids regulate domain establishment and maintenance involves lipid ordered membrane domains known as lipid rafts (reviewed in [31]). Lipid rafts are enriched in glycosphingolipids and have been implicated in a variety of cellular functions including signal transduction, intercellular adhesion and specific protein sequestering and sorting [32][33][34][35][36][37]. Although lipid rafts may play a role in molecular sorting and ultimately in domain formation and maintenance, it is unclear how certain proteins are included while others are excluded.…”

Section: Animal Modelmentioning

confidence: 99%

Compromised Myelin and Axonal Molecular Organization Following Adult-Onset Sulfatide Depletion

Dustin,

Suarez-Pozos,

Stotesberry

et al. 2023

Biomedicines

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3-O-sulfogalactosylceramide, or sulfatide, is a prominent myelin glycosphingolipid reduced in the normal appearing white matter (NAWM) in Multiple Sclerosis (MS), indicating that sulfatide reduction precedes demyelination. Using a mouse model that is constitutively depleted of sulfatide, we previously demonstrated that sulfatide is essential during development for the establishment and maintenance of myelin and axonal integrity and for the stable tethering of certain myelin proteins in the sheath. Here, using an adult-onset depletion model of sulfatide, we employ a combination of ultrastructural, immunohistochemical and biochemical approaches to analyze the consequence of sulfatide depletion from the adult CNS. Our findings show a progressive loss of axonal protein domain organization, which is accompanied by axonal degeneration, with myelin sparing. Similar to our previous work, we also observe differential myelin protein anchoring stabilities that are both sulfatide dependent and independent. Most notably, stable anchoring of neurofascin155, a myelin paranodal protein that binds the axonal paranodal complex of contactin/Caspr1, requires sulfatide. Together, our findings show that adult-onset sulfatide depletion, independent of demyelination, is sufficient to trigger progressive axonal degeneration. Although the pathologic mechanism is unknown, we propose that sulfatide is required for maintaining myelin organization and subsequent myelin–axon interactions and disruptions in these interactions results in compromised axon structure and function.

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