Details

Autor(en) / Beteiligte

• Egawa, Junji
• Pearn, Matthew L.
• Lemkuil, Brian P.
• Patel, Piyush M.
• Head, Brian P.

Titel

Membrane lipid rafts and neurobiology: age‐related changes in membrane lipids and loss of neuronal function

Ist Teil von

• The Journal of physiology, 2016-08, Vol.594 (16), p.4565-4579

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2016

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein‐coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age‐related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes. Summary illustrating how age‐related changes in the biochemistry and biophysical properties of the neuronal plasma membrane decrease MLRs, Cav‐1 expression, and MLR‐localized expression of neuronal receptors necessary for plasticity. A, normal adult neuronal plasma membranes (PMs) have an asymmetric cholesterol distribution (∼85% in the cytofacial and ∼15% in the exofacial leaflet), GM1 gangliosides in the exofacial leaflet, functional MLR microdomains, normal expression of Cav‐1 and MLR‐localized functional receptors necessary for growth and plasticity. B, during the ageing process, neuronal PMs exhibit a redistribution of cholesterol from the cytofacial to the exofacial leaflet, decreased GM1 gangliosides in the exofacial leaflet, loss of MLRs, decreased Cav‐1 protein expression, and decreased receptor localization to MLRs, thus reducing the ability to evoke plasticity to an ever changing environment.