Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding.
Members of the phosducin gene family were initially proposed to act as down-regulators of G protein signaling by binding G protein betagamma dimers (Gbetagamma) and inhibiting their ability to interact with G protein alpha subunits (Galpha) and effectors. However, recent findings have over-turned this hypothesis by showing that most members of the phosducin family act as co-chaperones with the cytosolic chaperonin complex (CCT) to assist in the folding of a variety of proteins from their nascent polypeptides. In fact rather than inhibiting G protein pathways, phosducin-like protein 1 (PhLP1) has been shown to be essential for G protein signaling by catalyzing the folding and assembly of the Gbetagamma dimer. PhLP2 and PhLP3 have no role in G protein signaling, but they appear to assist in the folding of proteins essential in regulating cell cycle progression as well as actin and tubulin. Phosducin itself is the only family member that does not participate with CCT in protein folding, but it is believed to have a specific role in visual signal transduction to chaperone Gbetagamma subunits as they translocate to and from the outer and inner segments of photoreceptor cells during light-adaptation.
Willardson
Barry M
BM
Department of Chemistry and Biochemistry, C-100 BNSN, Brigham Young University Provo, Utah 84602, USA. bmwillardson@chem.byu.edu
Howlett
Alyson C
AC
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D020555:GTP-Binding Protein Regulators / Q000737:chemistry / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D012160:Retina / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism; D014785:Vision, Ocular
D000199:Actins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005136:Eye Proteins; C118981:G-protein Beta gamma; D020555:GTP-Binding Protein Regulators; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C098789:PDCL protein, human; C498321:PDCL2 protein, human; C498322:PDCL3 protein, human; D010750:Phosphoproteins; D014404:Tubulin; C065631:phosducin; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins