Nanoscale regulation of Ca2+ dependent phase transitions and real-time dynamics of SAP97/hDLG

Premchand Rajeev, Nivedita Singh, Adel Kechkar, Cory Butler, Narendrakumar Ramanan, Jean-Baptiste Sibarita, Mini Jose, Deepak Nair
Nat Commun. 2022-07-22; 13(1):
DOI: 10.1038/s41467-022-31912-1

Synapse associated protein-97/Human Disk Large (SAP97/hDLG) is a conserved, alternatively spliced, modular, scaffolding protein critical in regulating the molecular organization of cell-cell junctions in vertebrates. We confirm that the molecular determinants of first order phase transition of SAP97/hDLG is controlled by morpho-functional changes in its nanoscale organization. Furthermore, the nanoscale molecular signatures of these signalling islands and phase transitions are altered in response to changes in cytosolic Ca2+. Additionally, exchange kinetics of alternatively spliced isoforms of the intrinsically disordered region in SAP97/hDLG C-terminus shows differential sensitivities to Ca2+ bound Calmodulin, affirming that the molecular signatures of local phase transitions of SAP97/hDLG depends on their nanoscale heterogeneity and compositionality of isoforms.

Auteurs Bordeaux Neurocampus