14-3-3 proteins in membrane protein transport

TY - JOUR

T1 - 14-3-3 proteins in membrane protein transport

AU - Mrowiec, Thomas

AU - Schwappach, Blanche

PY - 2006/9

Y1 - 2006/9

N2 - 14-3-3 proteins affect the cell surface expression of several unrelated cargo membrane proteins, e.g., MHC II invariant chain, the two-pore potassium channels KCNK3 and KCNK9, and a number of different reporter proteins exposing Arg-based endoplasmic reticulum localization signals in mammalian and yeast cells. These multimeric membrane proteins have a common feature in that they all expose coatomer protein complex I (COPI)- and 14-3-3-binding motifs. 14-3-3 binding depends on phosphorylation of the membrane protein in some and on multimerization of the membrane protein in other cases. Evidence from mutant proteins that are unable to interact with either COPI or 14-3-3 and from yeast cells with an altered 14-3-3 content suggests that 14-3-3 proteins affect forward transport in the secretory pathway. Mechanistically, this could be explained by clamping, masking, or scaffolding. In the clamping mechanism, 14-3-3 binding alters the conformation of the signal-exposing tail of the membrane protein, whereas masking or scaffolding would abolish or allow the interaction of the membrane protein with other proteins or complexes. Interaction partners identified as putative 14-3-3 binding partners in affinity purification approaches constitute a pool of candidate proteins for downstream effectors, such as coat components, coat recruitment GTPases, Rab GTPases, GTPase-activating proteins (GAPs), guanine-nucleotide exchange factors (GEFs) and motor proteins.

AB - 14-3-3 proteins affect the cell surface expression of several unrelated cargo membrane proteins, e.g., MHC II invariant chain, the two-pore potassium channels KCNK3 and KCNK9, and a number of different reporter proteins exposing Arg-based endoplasmic reticulum localization signals in mammalian and yeast cells. These multimeric membrane proteins have a common feature in that they all expose coatomer protein complex I (COPI)- and 14-3-3-binding motifs. 14-3-3 binding depends on phosphorylation of the membrane protein in some and on multimerization of the membrane protein in other cases. Evidence from mutant proteins that are unable to interact with either COPI or 14-3-3 and from yeast cells with an altered 14-3-3 content suggests that 14-3-3 proteins affect forward transport in the secretory pathway. Mechanistically, this could be explained by clamping, masking, or scaffolding. In the clamping mechanism, 14-3-3 binding alters the conformation of the signal-exposing tail of the membrane protein, whereas masking or scaffolding would abolish or allow the interaction of the membrane protein with other proteins or complexes. Interaction partners identified as putative 14-3-3 binding partners in affinity purification approaches constitute a pool of candidate proteins for downstream effectors, such as coat components, coat recruitment GTPases, Rab GTPases, GTPase-activating proteins (GAPs), guanine-nucleotide exchange factors (GEFs) and motor proteins.

KW - 14-3-3 Proteins/metabolism

KW - Cell Membrane/metabolism

KW - Humans

KW - Membrane Proteins/metabolism

KW - Protein Binding

KW - Protein Transport/physiology

U2 - 10.1515/BC.2006.152

DO - 10.1515/BC.2006.152

M3 - SCORING: Review article

C2 - 16972791

VL - 387

SP - 1227

EP - 1236

JO - BIOL CHEM

JF - BIOL CHEM

SN - 1431-6730

IS - 9

ER -