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

Premchand Rajeev, Nivedita Singh, Adel Kechkar, Corey Butler, Narendrakumar Ramanan, Jean-Baptiste Sibarita, Mini Jose and Deepak Nair ()
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Premchand Rajeev: Indian Institute of Science
Nivedita Singh: Indian Institute of Science
Adel Kechkar: Ecole Nationale Supérieure de Biotechnologie
Corey Butler: Université Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297
Narendrakumar Ramanan: Indian Institute of Science
Jean-Baptiste Sibarita: Université Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297
Mini Jose: Indian Institute of Science
Deepak Nair: Indian Institute of Science

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31912-1

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