AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP. 2018

Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

Ca2+-permeable AMPA-type glutamate receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits contribute to multiple forms of synaptic plasticity, including long-term potentiation (LTP), but mechanisms regulating CP-AMPARs are poorly understood. A-kinase anchoring protein (AKAP) 150 scaffolds kinases and phosphatases to regulate GluA1 phosphorylation and trafficking, and trafficking of AKAP150 itself is modulated by palmitoylation on two Cys residues. Here, we developed a palmitoylation-deficient knockin mouse to show that AKAP150 palmitoylation regulates CP-AMPAR incorporation at hippocampal synapses. Using biochemical, super-resolution imaging, and electrophysiological approaches, we found that palmitoylation promotes AKAP150 localization to recycling endosomes and the postsynaptic density (PSD) to limit CP-AMPAR basal synaptic incorporation. In addition, we found that AKAP150 palmitoylation is required for LTP induced by weaker stimulation that recruits CP-AMPARs to synapses but not stronger stimulation that recruits GluA2-containing AMPARs. Thus, AKAP150 palmitoylation controls its subcellular localization to maintain proper basal and activity-dependent regulation of synaptic AMPAR subunit composition.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D011992 Endosomes Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Receptosomes,Endosome,Receptosome
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse
D017774 Long-Term Potentiation A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. Long Term Potentiation,Long-Term Potentiations,Potentiation, Long-Term,Potentiations, Long-Term
D049229 Dendritic Spines Spiny processes on DENDRITES, each of which receives excitatory input from one nerve ending (NERVE ENDINGS). They are commonly found on PURKINJE CELLS and PYRAMIDAL CELLS. Dendritic Spine,Spine, Dendritic,Spines, Dendritic
D054758 A Kinase Anchor Proteins A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA. A-Kinase Anchoring Protein,A-Kinase Anchoring Proteins,A-Kinase Anchor Proteins,Protein Kinase A Anchor Proteins,A Kinase Anchoring Protein,A Kinase Anchoring Proteins,Anchor Proteins, A-Kinase,Anchoring Protein, A-Kinase,Protein, A-Kinase Anchoring

Related Publications

Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
October 2012, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
May 2010, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
October 2021, Cell reports,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
June 1996, Nature,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
June 2006, Current opinion in neurobiology,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
July 2014, PLoS biology,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
March 2007, Trends in neurosciences,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
May 2001, Japanese journal of pharmacology,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
April 2016, Science signaling,
Alicia M Purkey, and Kevin M Woolfrey, and Kevin C Crosby, and Dominik G Stich, and Wallace S Chick, and Jason Aoto, and Mark L Dell'Acqua
December 2021, Molecular neurobiology,
Copied contents to your clipboard!