Details

Autor(en) / Beteiligte

• Bermudez, I
• Moronl, M

Titel

Phosphorylation and Function of alpha 4 beta 2 Receptor

Ist Teil von

• Journal of molecular neuroscience, 2006-09, Vol.30 (1-2), p.97-98

Erscheinungsjahr

2006

Quelle

SpringerLink Journals

Beschreibungen/Notizen

• The neuronal nicotinic acetylcholine receptor (nAChR) alpha 4 and beta 2 subunits expressed in heterologous expression systems assemble into high- and lowaffinity receptors (Zwart and Vijverberg, 1998; Buisson and Bertrand, 2001; Houlihan et al., 2001; Nelson et al., 2003), which reflects the assembly of two distinct subunit stoichlometries of alpha 4 beta 2 receptor (Nelson et al., 2003). The high-affinity receptor ([ alpha 4]2 [ beta 2]3) is about 100-fold more sensitive to ACh than the lowaffinity receptor ([ alpha 4]3[ beta 2]2) (Zwart and Vijverberg, 1998; Buisson and Bertrand, 2001; Houlihan et al., 2001; Nelson et al., 2003). Recent evidence implicated 14-3-3 proteins as modulators of the relative abundance of nAChR subunits in the endoplasmic reticulum (ER), where ligand-gated ion channels assemble. The 14-3-3 proteins influence ER-to-plasma membrane trafficking of multimeric cell-surface proteins (O'Kelly et al., 2002). 14-3-3 proteins bind components of these multimeric proteins, and this interaction overrides dibasic COP1 retention signal to permit forward transport of the protein (O'Kelly et al., 2002). In the case of alpha 4 beta 2 nAChRs, 14-3-3 binds the alpha 4 subunit, and this association is dependent on phosphorylation of a serine residue within a protein kinase A(PKA) consensus sequence in the large cytoplasmic domain of the alpha 4 subunit, which is also a binding motif recognized by 14-3-3 (Jeancloss et al., 2001; O'Kelly et al., 2002). The interplay among PKA, alpha 4 subunits, and 14-3-3 proteins increases cell-surface expression of alpha 4 beta 2 nAChRs by increasing steady-state levels of the alpha 4 subunit available for assembly with beta 2 subunits (Jeancloss et al., 2001). Because it is not known how 14-3-3-dependent changes in the steady-state levels of the alpha 4 subunit might affect the functional type of alpha 4 beta 2 receptors, we have investigated the effects of mutations of the 14-3-3 binding motif in the a4 subunit on alpha 4 beta 2 nAChR function.