Genetically encoded fluorescent sensors for glycine and D-serine detection

PI: Laura Caldinelli and Loredano Pollegioni

Participants:
Gianluca Molla

Publications:

• Rosini et al., 2020. Biosensors for D-amino acids: detection methods and applications. Int J Mol Sci., 21:4574. Doi: 10.3390/ijms21134574. 

• Pollegioni and Sacchi, 2010. Metabolism of the neuromodulator
  D-serine. Cell Mol Life Sci., 67:2387-2404. Doi: 10.1007/s00018-010-0307-9. 

Fundings:

Not funded

Collaborations:

Jean-Pierre MOTHET
CNRS - ENS Paris Saclay - Gif-sur-Yvette, FR

The activation of the NMDA receptors (NMDAR) involves the simultaneous binding of glutamate and of a co-agonist, which can be glycine or D-serine. Altered concentration of these neurotransmitters

causes NMDAR dysfunction resulting in neurological disorders:

• an overstimulation of NMDAR is involved in stroke, epilepsy, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and major depressive disorder;

• a downregulation of NMDAR is 
  involved in schizophrenia and attention deficit hyperactivity disorder.

This project is aimed to develop two genetically encoded fluorescent biosensors highly specific for  glycine and D-serine, which can be exploited to assay the concentration of these two neurotransmitters into living cells.

Genetically encoded fluorescent  biosensors developed during this project will be expressed in cultured neurons and in animal brain in order to assay the concentration of these two signaling molecules in vivo and thus to assess alterations due to pathological mechanisms or therapeutic treatments.