Subcellular localization of Rap1 GTPase activator CalDAG-GEFI is orchestrated by interaction of its atypical C1 domain with membrane phosphoinositides.

ABSTRACT:

Background

The small GTPase Rap1 and its guanine nucleotide exchange factor, CalDAG-GEFI (CDGI), are critical for platelet function and hemostatic plug formation. CDGI function is regulated by a calcium binding EF hand regulatory domain and an atypical C1 domain with unknown function.

Objective

Here, we investigated whether the C1 domain controls CDGI subcellular localization, both in vitro and in vivo.

Methods

CDGI interaction with phosphoinositides was studied by lipid co-sedimentation assays and molecular dynamics simulations. Cellular localization of CDGI was studied in heterologous cells by immunofluorescence and subcellular fractionation assays.

Results

Lipid co-sedimentation studies demonstrated that the CDGI C1 domain associates with membranes through e

SUBMITTER: Sarker M 

PROVIDER: S-EPMC7050387 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature