LTP and LTD: an embarrassment of riches.

Seven-transmembrane receptors, which constitute the largest, most ubiquitous and most versatile family of membrane receptors, are also the most common target of therapeutic drugs. Recent findings indicate that the classical models of G-protein coupling and activation of second-messenger-generating enzymes do not fully explain their remarkably diverse biological actions.

Seven-transmembrane receptors.

Synaptic plasticity: multiple forms, functions, and mechanisms.

http://www.somosbacteriasyvirus.com/powerhouse.pdf

Mitochondria: more than just a powerhouse.

PDZ domains are protein-interaction domains that are often found in multi-domain scaffolding proteins. PDZ-containing scaffolds assemble specific proteins into large molecular complexes at defined locations in the cell. In the postsynaptic density of neuronal excitatory synapses, PDZ proteins such as PSD-95 organize glutamate receptors and their associated signalling proteins and determine the size and strength of synapses. PDZ scaffolds also function in the dynamic trafficking of synaptic proteins by assembling cargo complexes for transport by molecular motors. As key organizers that control synaptic protein composition and structure, PDZ scaffolds are themselves highly regulated by synthesis and degradation, subcellular distribution and post-translational modification.

/pdf/pdz-domain-proteins-of-synapses-2oiarur8tc.pdf

PDZ domain proteins of synapses

https://faculty.washington.edu/scottjdw/pdfs/colledge_neuron_2003_p595.pdf

Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression.

The Scar/WAVE family of scaffolding proteins organize molecular networks that relay signals from the GTPase Rac to the actin cytoskeleton. The WAVE-1 isoform is a brain-specific protein expressed in variety of areas including the regions of the hippocampus and the Purkinje cells of the cerebellum. Targeted disruption of the WAVE-1 gene generated mice with reduced anxiety, sensorimotor retardation, and deficits in hippocampal-dependent learning and memory. These sensorimotor and cognitive deficits are analogous to the symptoms of patients with 3p-syndrome mental retardation who are haploinsufficient for WRP/MEGAP, a component of the WAVE-1 signaling network. Thus WAVE-1 is required for normal neural functioning.

Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice

A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase (PKA) and other signaling enzymes to distinct subcellular organelles. Using the yeast two-hybrid approach, we demonstrate that Rab32, a member of the Ras superfamily of small molecular weight G-proteins, interacts directly with the type II regulatory subunit of PKA. Cellular and biochemical studies confirm that Rab32 functions as an AKAP inside cells. Anchoring determinants for PKA have been mapped to sites within the conserved α5 helix that is common to all Rab family members. Subcellular fractionation and immunofluorescent approaches indicate that Rab32 and a proportion of the cellular PKA pool are associated with mitochondria. Transient transfection of a GTP binding–deficient mutant of Rab32 promotes aberrant accumulation of mitochondria at the microtubule organizing center. Further analysis of this mutant indicates that disruption of the microtubule cytoskeleton results in aberrantly elongated mitochondria. This implicates Rab32 as a participant in synchronization of mitochondrial fission. Thus, Rab32 is a dual function protein that participates in both mitochondrial anchoring of PKA and mitochondrial dynamics.

https://rupress.org/jcb/article-pdf/158/4/659/1306750/jcb1584659.pdf

Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.

https://faculty.washington.edu/scottjdw/pdfs/diviani_jbc_2001_p44247.pdf

AKAP-Lbc Anchors Protein Kinase A and Nucleates Gα12-selective Rho-mediated Stress Fiber Formation

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Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression.

Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice

Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.

AKAP-Lbc Anchors Protein Kinase A and Nucleates Gα12-selective Rho-mediated Stress Fiber Formation