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The PDZ and Band 4.1 containing protein Frmpd1 influences the subcellular location of Activator of G‐ protein signaling 3 and its interaction with G‐proteins
Author(s) -
An Ningfei,
Blumer Joe B.,
Lanier Stephen M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.908.4
Subject(s) - pdz domain , microbiology and biotechnology , biology , ferm domain , membrane protein , cell membrane , activator (genetics) , transport protein , cell , receptor , biochemistry , integral membrane protein , membrane
Activator of G protein signaling 3 (AGS3) contains seven tetratricopeptide (TPR) motifs upstream of four G‐protein regulatory (GPR) motifs, each of which can serve as a docking site for GiαGDP free of Gβγ. Such proteins have revealed unexpected functional diversity for the “G‐switch” in the control of events within the cell independent of the role of G‐proteins as transducers for G‐protein coupled receptors at the cell surface. A key question is what controls their subcellular positioning and interaction with G‐proteins. Frmpd1, which contains a PDZ and a FERM domain was identified as an AGS3‐TPR domain binding partner in yeast 2‐hybrid screens. Following co‐transfection of COS7 cells, Frmpd1 increased the amount of AGS3 associated with a membrane fraction following cell lysis. The increase in membrane‐associated AGS3 likely reflects both retention of AGS3 that is lost during membrane washing and the preferred positioning of AGS3 in a membrane fraction when complexed with Frmpd1. The interaction of AGS3 with Frmpd1 and Giα3 is mutually exclusive. Frmpd1 and AGS3 are both expressed in the neuronal catecholaminergic cell line CAD. siRNA‐mediated knock down of Frmpd1 resulted in a ~50% decrease in the amount of AGS3 associated with the membrane fraction following cell lysis. Mechanistically, Frmpd1 may stabilize AGS3 at the plasma membrane and influence the interaction of AGS3 with G protein.