RT Journal Article
SR Electronic
T1 The synaptic vesicle protein Mover/TPRG1L is associated with lipid droplets in astrocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.18.476809
DO 10.1101/2022.01.18.476809
A1 Jeremy Krohn
A1 Florelle Domart
A1 Thanh Thao Do
A1 Thomas Dresbach
YR 2022
UL http://biorxiv.org/content/early/2022/01/21/2022.01.18.476809.abstract
AB Crucial brain functions such as neurotransmission, myelination, and signaling pose a high demand for lipids. Lipid dysregulation is associated with neuroinflammation and neurodegeneration. Astrocytes protect neurons from lipid induced damage by accumulating and metabolizing toxic lipids in organelles called lipid droplets (LDs). LDs have long been considered as lipid storage compartments in adipocytes, but less is known about their biogenesis and composition in the brain. In particular, proteins covering the LD surface are not yet fully identified.Here, we report that the synaptic vesicle protein Mover/TPRG1L, which regulates the probability of neurotransmitter release in neurons, is a component of the LD coat in astrocytes. Using conventional and super resolution microscopy, we demonstrate that Mover surrounds naive and oleic acid induced astrocytic LDs. We confirm the identity of astrocytic LDs using the neutral lipid stains Bodipy and LipidTox, as well as immunofluorescence for perilipin-2, a known component of the LD coat. In astrocytes, recombinant Mover was sufficient to induce an accumulation of LDs. Furthermore, we identified point mutations that abolish targeting to LDs and show similarities in the required binding sequences for association to the presynapse and LDs.Our results show that Mover is not only a presynaptic protein but also a candidate for LD regulation. This highlights the dual role of Mover in synaptic transmission and regulation of astrocytic LDs, which may be particularly important in the context of lipid-related neurological disorders.Main points- Mover is a lipid droplet protein- Overexpression of Mover drives lipid droplet accumulation- The F206 is important for LD targetingCompeting Interest StatementThe authors have declared no competing interest.