Cardiac CD47 drives left ventricular heart failure through Ca2+-CaMKII-regulated induction of HDAC3.

Background: Left ventricular heart failure (LVHF) remains progressive and fatal and is a formidable health problem because ever-larger numbers of people are diagnosed with this disease. Therapeutics, while relieving symptoms and extending life in some cases, cannot resolve this process and transplant remains the option of last resort for many. Our team has described a widely expressed cell surface receptor (CD47) that is activated by its high-affinity secreted ligand, thrombospondin 1 (TSP1), in acute injury and chronic disease; however, a role for activated CD47 in LVHF has not previously been proposed.

A biochemical and functional protein complex involving dopamine synthesis and transport into synaptic vesicles.

Synaptic transmission depends on neurotransmitter pools stored within vesicles that undergo regulated exocytosis. In the brain, the vesicular monoamine transporter-2 (VMAT(2)) is responsible for the loading of dopamine (DA) and other monoamines into synaptic vesicles. Prior to storage within vesicles, DA synthesis occurs at the synaptic terminal in a two-step enzymatic process.

The molecular chaperone Hsc70 interacts with the vesicular monoamine transporter-2.

Synaptic transmission depends on the efficient loading of transmitters into synaptic vesicles by vesicular neurotransmitter transporters. The vesicular monoamine transporter-2 (VMAT2) is essential for loading monoamines into vesicles and maintaining normal neurotransmission. In an effort to understand the regulatory mechanisms associated with VMAT2, we have embarked upon a systematic search for interacting proteins.

Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3.

Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system.

The orphan transporter Rxt1/NTT4 (SLC6A17) functions as a synaptic vesicle amino acid transporter selective for proline, glycine, leucine, and alanine.

Rxt1/NTT4 (SLC6A17) belongs to a gene family of "orphan transporters" whose substrates and consequently functions remain unidentified. Although Rxt1/NTT4 was previously thought to function as a sodium-dependent plasma membrane transporter, recent studies localized the protein to synaptic vesicles of glutamatergic and GABAergic neurons. Here, we provide evidence indicating that Rxt1/NTT4 functions as a vesicular transporter selective for proline, glycine, leucine, and alanine.

ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory.

The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell morphogenesis and migration in vivo.

Requirement for Abl kinases in T cell receptor signaling.

Background: The c-Abl and Arg proteins comprise a unique family of nonreceptor tyrosine kinases that have been implicated in the regulation of cell proliferation and survival, cytoskeletal reorganization, cell migration, and the response to oxidative stress and DNA damage. Targeted deletion or mutation of c-Abl in mice results in a variety of immune system phenotypes, including splenic and thymic atrophy, lymphopenia, and an increased susceptibility to infection. However, despite the generation of these mice over a decade ago, little is known regarding the mechanisms responsible for these phenotypes or the immune-related consequences of ablation of both the c-Abl and Arg kinases, which are coexpressed in lymphoid tissues.

Elevated expression of a subset of interferon inducible genes in primary bone marrow cells expressing p185 Bcr-Abl versus p210 Bcr-Abl by DNA microarray analysis.

p185 Bcr-Abl has a more aggressive biological/clinical leukemia phenotype than p210 Bcr-Abl. In this study, we examined differential gene expression using microarrays to determine if upregulation or downregulation of specific genes may explain the distinct phenotypes produced by the two Bcr-Abl forms. RNA was collected from mouse bone marrow mononuclear cells expressing equivalent levels of p185 or p210, and the RNAs were subjected to microarray analysis.