The anti-apoptotic response of the Gq/11-coupled muscarinic receptor family.
It is now clear that G-protein-coupled receptors can regulate programmed cell death (apoptosis) through a variety of mechanisms that are dependent on cell type and receptor subtype. Here we present evidence that the G(q/11)-coupled subtypes of the muscarinic receptor family (namely M(1), M(3) and M(5)-muscarinic receptor subtypes) are able to protect against apoptotic cell death. In particular we demonstrate that the C-terminal tail of the M(3)-muscarinic receptor is an essential structural element for signalling to the anti-apoptotic pathway. Removal of the distal portion of the C-terminal tail results in a receptor that is coupled normally to the G(q/11)/phospholipase C pathway and the mitogen-activated protein kinase pathway, but is unable to couple to the anti-apoptotic pathway. Furthermore, a poly-basic region conserved within the C-terminal tail of the G(q/11)-coupled muscarinic receptor subtypes appears to be the structural determinant of coupling to the anti-apoptotic pathway.
Tobin
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AB
Department of Cell Physiology and Pharmacology, Hodgkin Building, Lancaster Road, University of Leicester, Leicester LE1 9HN, U.K. tba@le.ac.uk
Budd
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DC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2; D011976:Receptors, Muscarinic; D043802:GTP-Binding Protein alpha Subunits, Gq-G11