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

Nat Commun. 2022 Jul 22;13(1):4236. doi: 10.1038/s41467-022-31912-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Calcium / metabolism*
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Discs Large Homolog 1 Protein / metabolism*
  • Humans
  • Membrane Proteins* / metabolism
  • Protein Isoforms / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Calmodulin
  • DLG1 protein, human
  • Discs Large Homolog 1 Protein
  • Membrane Proteins
  • Protein Isoforms
  • Calcium