Quantitative and functional assessment of Arc n-meric states in membrane interaction and AMPA receptor endocytosis

• Arc (or Arg3.1), Activity Regulated-Cytoskeleton associated-protein is pivotal to mediate plastic responses in neuronal cells. In vitro and in vivo studies suggest its ability to form high- and low-order oligomers which are potentially involved in neuronal trafficking. Despite its important function, no direct observation of Arc oligomers in cells has been presented due to its highly regulated spatiotemporal expression, the small size of the structures, the lack of appropriate labelling strategies and the background associated to free diffusing cytosolic proteins. Here, we take advantage of several complementary advanced fluorescence microscopy and spectroscopy techniques to observe and quantify Arc oligomeric states in cellular environment especially in the synapses. In cells, we uncovered Arc-Arc intermolecular interactions, Arc tendency to form liquid condensates and to interact with lipid bilayers. High-order oligomers are found to localize at the excitatory synaptic compartment and to directly affects AMPA receptor surface levels. Together, our observations support the model by which Arc oligomerization mediates plasma- membrane negative inward curvature favoring AMPA receptors endocytosis.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Arc (Activity-regulated cytoskeleton-associated protein)

AMPA receptors

oligomerization

STED

FCS

DNA-PAINT

STARSS

molecular dynamics simulations.

Biological and Biomedical Physics

Biologisk och biomedicinsk fysik

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)