Dysbindin-associated proteome in the p2 synaptosome fraction of mouse brain.

The gene DTNBP1 encodes the protein dysbindin and is among the most promising and highly investigated schizophrenia-risk genes. Accumulating evidence suggests that dysbindin plays an important role in the regulation of neuroplasticity. Dysbindin was reported to be a stable component of BLOC-1 complex in the cytosol.

The novel caspase-3 substrate Gap43 is involved in AMPA receptor endocytosis and long-term depression.

The cysteine protease caspase-3, best known as an executioner of cell death in apoptosis, also plays a non-apoptotic role in N-methyl-d-aspartate receptor-dependent long-term depression of synaptic transmission (NMDAR-LTD) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor endocytosis in neurons. The mechanism by which caspase-3 regulates LTD and AMPA receptor endocytosis, however, remains unclear. Here, we addressed this question by using an enzymatic N-terminal peptide enrichment method and mass spectrometry to identify caspase-3 substrates in neurons.

Proteomics analysis reveals overlapping functions of clustered protocadherins.

The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-alpha, Pcdh-beta, and Pcdh-gamma, play important roles in the development of the vertebrate central nervous system. To gain insight into the molecular action of PCDHs, we performed a systematic proteomics analysis of PCDH-gamma-associated protein complexes. We identified a list of 154 non-redundant proteins in the PCDH-gamma complexes.

alpha- and gamma-Protocadherins negatively regulate PYK2.

Genetic studies demonstrate that gamma-protocadherins (PCDH-gamma) are required for the survival and synaptic connectivity in neuronal subpopulations of the central nervous system. However, the intracellular signaling mechanisms for PCDH-gamma are poorly understood. Here, we show that PCDH-gamma binds two tyrosine kinases, PYK2 and focal adhesion kinase (FAK), and interaction with PCDH-gamma inhibits kinase activity.

The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri-miRNA by DCL1.

The results of genetic studies in Arabidopsis indicate that three proteins, the RNase III DICER-Like1 (DCL1), the dsRNA-binding protein HYPONASTIC LEAVES1 (HYL1), and the C2H2 Zn-finger protein SERRATE (SE), are required for the accurate processing of microRNA (miRNA) precursors in the plant cell nucleus. To elucidate the biochemical mechanism of miRNA processing, we developed an in vitro miRNA processing assay using purified recombinant proteins. We find that DCL1 alone releases 21-nt short RNAs from dsRNA as well as synthetic miR167b precursor RNAs.

Arabidopsis primary microRNA processing proteins HYL1 and DCL1 define a nuclear body distinct from the Cajal body.

Small regulatory microRNAs (miRNAs) are encoded in long precursors and are released from them during processing by cleavage within partially duplexed stem-loop structures. In the present work we investigated the role of the Arabidopsis nuclear RNA-binding protein HYL1 and the nuclear RNase III enzyme DCL1 in processing of primary miRNA (pri-miR171a). The miR171a gene is complex, with multiple transcription start sites, as well as alternative splicing of exons and alternative polyadenylation sites.

The Arabidopsis double-stranded RNA-binding protein HYL1 plays a role in microRNA-mediated gene regulation.

The Arabidopsis HYL1 gene encodes a nuclear double-stranded RNA-binding protein. A knockout mutation of the hyl1 gene is recessive and pleiotropic, causing developmental abnormalities, increasing sensitivity to abscisic acid, and reducing sensitivity to auxin and cytokinin. We report that levels of several microRNAs (miRNAs; miR159, -167, and -171) are reduced in homozygous mutant plants, and levels of two of three tested target mRNAs are elevated.